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At least 757 records · Page 42Linked to original sources
PubMed2006

Non-random associations and vascular fields in neurofibromatosis 1: a pathogenetic hypothesis.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with highly variable expression generally ascribed to random factors. However, evidence is presented for patterns suggesting non-stochastic processes as follows: (1) We have seen a MZ twin pair concordant for renal vascular hypertension, and another for unilateral ptosis. Other concordances have been reported, including both malformations and tumors, and combinations as well. (2) Four children were seen with a distinct ipsilateral association of glaucoma or iris anomaly, optic glioma, plexiform neurofibromas arising from the trigeminal nerve and its branches, and sphenoid dysplasia. Other cases in the literature support milder forms of this association. (3) We saw six children with apparent gynecomastia or premature thelarche without endocrine abnormalities. Tissue samples from four of these showed an unusual fibrous plexiform neurofibroma. Interestingly, five of the six cases were African Americans, and constitutional factors affecting fibrous reactions may also be involved here.A tentative hypothesis is presented suggesting vascular fields involving defined areas that can: (1) Support tumor growth. They would be the "soil" determining the ability and the extent of growth. There would, however, still be a need for a "second hit" tumor transformation. (2) Affect blood supply to organs, creating structural anomalies. NF1 involves a vasculopathy, and would predispose to vulnerabilities of such fields. Genetic factors could induce superimposed susceptibilities of specific fields, leading to twin concordances. "Hits" affecting specific fields would increase the likelihood of multiple abnormalities that could include both tumors and structural findings. Finally, tumors may follow the contours of existing fields. The breast is an area normally primed for growth, and the observation of clitoromegally secondary to tumor involvement suggests that such fields exist elsewhere.

Child↗
PubMed1996

Significance of NO in hemorrhage-induced hemodynamic alterations, organ injury, and mortality in rats.

In an attempt to evaluate the role of nitric oxide (NO) in pathophysiological alterations and multiple organ damage caused by hemorrhagic shock, we employed NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, in anesthetized rats subjected to a prolonged hypovolemic insult (30-35 mmHg for 180 min). Infusion of 2.0 mg/kg L-NMMA at the end of resuscitation diminished the fall in mean arterial pressure (MAP) and significantly increased the cardiac index and stroke volume, together with remarkable protection from multiple organ damage compared with the controls. The 48-h survival rate was significantly improved from 26.7% in the control group to 68.8% in the treatment group (P < 0.05). In contrast, the high dose of 20.0 mg/kg L-NMMA resulted in a strong blood pressure response, but a marked reduction in cardiac index and stroke volume concomitant with an increased total peripheral resistance index within the observation period, and tended to increase damage to various organs at 2 h after treatment. In addition, marked elevation in both endotoxin and tumor necrosis factor levels were observed in animals subjected to shock insult. The results suggest that NO induced by hemorrhagic shock in rats is an important mediator for pathophysiological alterations associated with cardiovascular abnormalities, multiple organ dysfunction, and even lethality. Regulation of NO generation and use of NO inhibitors might provide new aspects in the treatment of hemorrhage-related disorders, whereas the administration of L-NMMA would be either deleterious or salutary in a dose-dependent manner.

Animals↗
PubMed1987

Diabetes and atherosclerosis: an epidemiologic view.

Diabetes is associated with changes in plasma lipids and lipoproteins into atherogenic direction. In IDDM these changes are small or absent if good metabolic control can be maintained. Diabetic nephropathy is, however, associated with the appearance of dyslipoproteinemia. In NIDDM plasma total and VLDL triglyceride levels are elevated, and HDL-cholesterol level is decreased, and this pattern of dyslipoproteinemia does not always respond to improved control of hyperglycemia. Abnormalities of lipoprotein metabolism, not reflected in conventional plasma lipid and lipoprotein level measurements, and glucosylation of lipoproteins and resulting alterations in lipoprotein catabolism may be of importance in the enhanced atherogenesis in diabetes. Both IDDM and NIDDM are associated with an increased frequency of hypertension, but the underlying mechanisms appear to be different. In IDDM hypertension is usually associated with the development of diabetic nephropathy and thus with a long duration of the disease. In NIDDM hypertension is often present already at the time of diagnosis, and also in IGT, the precursor stage of NIDDM, the prevalence of hypertension is already increased. Obesity explains only in part the high prevalence of hypertension in patients with NIDDM. Diabetes is known to be associated with multiple abnormalities in hemostatic factors and, although these abnormalities may contribute importantly to the increased risk of ASVD in diabetic patients, information about their real role is scanty and conflicting. The impact of general major risk factors for ASVD, elevated plasma cholesterol, elevated blood pressure, and smoking, on the risk of ASVD appears to be similar in diabetics and nondiabetics. Only a relatively small proportion of the excessive occurrence of ASVD in diabetics can, however, be explained by the effects of diabetes on the levels of general risk factors for ASVD. This proportion mediated through the effects of diabetes on risk factors is larger in female diabetics than in male diabetics. The major proportion of the excess of ASVD in diabetics remains, however, unexplained and must be due to effects of diabetes itself through mechanisms that are incompletely understood.

Arteriosclerosis↗
PubMed1991

Feline infectious peritonitis: a review of clinicopathological changes in 65 cases, and a critical assessment of their diagnostic value.

In 65 natural cases of feline infectious peritonitis (FIP) the common clinicopathological changes included lymphopenia (77 per cent), neutrophilia (45 per cent), anaemia (37 per cent), hyperproteinaemia (39 per cent) and hyperglobulinaemia (39 per cent). There was no difference in the frequency of these abnormalities between the 38 cases of effusive disease and the 27 cases of non-effusive disease. The most consistent changes shown by serum protein electrophoresis were increases in alpha 2- and gamma-globulins. The protein content of the effusions ranged from 39 to 98 g/litre with the globulins comprising 50 to 82 per cent. Coronavirus serology showed a wide variation in antibody titres (0 to 2560) with 320 the modal titre. The diagnostic value of this information was evaluated by comparing it with data from 65 cats in which FIP was considered as a differential diagnosis, but another disease was diagnosed. None of the laboratory tests, including coronavirus serology, had good sensitivity and specificity for the diagnosis of the disease. The presence of multiple abnormalities compatible with the disease increased the specificity but decreased the sensitivity of the diagnosis.

Anemia↗
PubMed1997

Male accessory sex organ morphogenesis is altered by loss of function of Hoxd-13.

The role of the Hox gene Hoxd-13 in postnatal morphogenesis of the male accessory sex organs was examined by correlating the distribution and temporal regulation of expression in the accessory sex organs of postnatal mice with morphologic abnormalities of Hoxd-13-deficient transgenic mice. Previous studies of Hoxd-13 expression in the perinatal period have shown a broad domain of expression in the lower genitourinary tract, with expression in both mesenchyme and epithelium; focal expression was also noted in the epithelium of the nascent ducts of the developing prostate. Quantitative RT-PCR studies of Hoxd-13 expression in the 5 day mouse confirm widespread expression in the accessory sex organs developing from both the Wolffian duct and the urogenital sinus. Expression is down-regulated with age, and a detailed time course of expression in the developing prostate shows that the level of Hoxd-13 expression correlates with morphogenetic activity in the development of the prostate ductal system. Transgenic Hoxd-13-deficient mice display multiple abnormalities in the male accessory sex organs. The most severe abnormalities were observed in organs exhibiting ductal branching during postnatal development and included diminished mesenchymal folding in the seminal vesicles, decreased size and diminished ductal branching in the ventral and dorsal prostate, and agenesis of the bulbourethral gland. We conclude that Hoxd-13 expression in the postnatal period correlates with a period of intense morphogenetic activity in accessory sex organ development and that the function of Hoxd-13 is evidenced by morphologic abnormalities in accessory sex organs of the Hoxd-13-deficient mutant.

Animals↗
PubMed1987

Wrinkly skin syndrome: phenotype and additional manifestations.

The wrinkly skin syndrome is an autosomal recessive disorder characterized by wrinkling of the skin of the dorsum of the hands and feet, decreased elastic recoil of the skin, an increased number of palmar and plantar creases, multiple musculoskeletal abnormalities, microcephaly, and mental retardation. Our patient is characteristic of the syndrome as previously described, and confirms the presence of mental retardation and microcephaly as component manifestations, with the additional findings of connective tissue abnormalities evidenced by an atrial septal aneurysm.

Abnormalities, Multiple↗
PubMed1991

Human acardiac anomaly: a report of three cases.

We report on three cases of acardia, all of which had to be classified as acardius anceps. The degree of cardiac malformation ranged between a completely missing heart and a malrotation of a relatively well-developed heart. One fetus showed an intermediate form of cardiac malformation with a hypoplastic cor triloculare. Our findings suggest that the defect in cardiac development may take place at different times in early embryogenesis, resulting in differing degrees of cardiac malformation.

Abnormalities, Multiple↗
PubMedDate not supplied

Morphological and cytogenetical changes in HR-18 rat ascites cells after in vitro 3-[bis(2-chloroethyl)amino]-4-methylbenzoic acid (NSC-146171; IOB-82) administration.

A bifunctional alkylating agent, 3-[Bis(2-chloroethyl) amino]-4-methylbenzoic acid (NSC-146171; IOB-82) was administered in HR-18 rat ascites cell cultures (which presented 2 morphologic cellular types: A and B type cells, genetically, 2 cellular populations having 41-45 and 85-86 chromosomes and cells with high ploidy), and the morphological and cytogenetical effects were related to the compound concentration. Thus, 24 h after IOB-82 administration in small doses (3.62 X 10(-4) micron/ml), important morphological changes were observed: nuclear changes (denuded nuclei, pyknosis) and cytoplasmic alterations (breaks at the exoplasm level, followed by cytoplasmic extrusions in extracellular spaces, cytoplasmic vacuolization). In addition to these changes, other abnormalities were observed when IOB-82 was administered in large doses (3.62 X 10(-3) micron/ml), i.e., nuclear changes (nuclear residues, granulation of the nuclear material and spreading of the nuclear content into cytoplasm) and cytoplasmic alterations (cytoplasmic shades and accentuated cytoplasmic vacuolization). Generally, the large A-type cells were more affected. Twenty-four h after IOB-82 treatment (with small or large doses), the chromatid and chromosome aberrations (gaps, breaks, deletions, fragments) were also observed. These aberrations were more numerous when IOB-82 was administered in large doses. Both morphological and cytogenetical changes indicate that the effect of IOB-82 could be radiomimetic. Changes produced and their incidence appear to depend on the concentration of IOB-82 employed and the morphological type of ascites cells. These are expressed in terms of multiple abnormality production in these cells. IOB-82 treatment produced changes in chromosome numbers and especially the disappearance of polyploid cells and cell populations with 85-86 chromosomes. These results indicate a possible correlation between the increased sensitivity of HR-18 rat ascites cells and changes in ploidy.

Animals↗
PubMed1996

Abnormal characteristics in young offspring of parents with non-insulin-dependent diabetes mellitus. The Bogalusa Heart Study.

Non-insulin-dependent (type II) diabetes has a strong familial component. In 1989-1991, a community-based study of young Caucasian offspring (mean age, 15.3 years) of non-insulin-dependent (type II) diabetics (n = 25) and nondiabetics (n = 27) representing 13 and 12 families, respectively, was conducted in Bogalusa, Louisiana, to determine whether metabolic abnormalities could be detected in early life. All offspring were given a 1-hour oral glucose tolerance test. The offspring of diabetics (versus nondiabetics) had significantly increased measures of body fatness; blood pressure; and fasting levels of glucose, insulin, glucagon, insulin-to C-peptide ratio, and triglycerides. The increases of systolic blood pressure, glucose, and glucagon remained significant after adjustment for differences in body mass index (BM). After glucose challenge, only plasma glucose response was significantly higher in the offspring of diabetics, even after controlling for differences in BMI. None of the offspring of nondiabetics had 30-minute (peak) glucose levels above 161 mg/dl (8.9 mmol/liter), compared with 41% of the offspring from diabetics. High glucose response and BMI were independently associated with parental diabetes. These results indicate that it is possible to identify multiple abnormalities in some offspring of type II diabetics at an early age that may presage the onset of overt adult diabetes.

Adipose Tissue↗
PubMedDate not supplied

Antenatal ultrasonic evaluation of acardiac monsters.

Acardiac monster represents a rare but serious complication of monozygotic twin pregnancy. Antenatal recognition is important because of accompanying obstetrical problems, including polyhydramnios, dystocia, and uterine rupture. While pathologic findings are varied, characteristic sonographic findings allow accurate prenatal diagnosis. Acardia must be distinguished from sacrococcygeal teratoma, omphalocele and macerated fetus.

Abnormalities, Multiple↗
PubMed2000

Familial hyperparathyroidism.

Familial hyperparathyroidism (HPT) is a hereditary disease in which HPT is transmitted in an autosomal dominant fashion. It includes a variety of diseases: multiple endocrine neoplasia (MEN) type 1 and type 2, and familial isolated hyperparathyroidism (FIHPT). We screened for MEN 1 mutations by direct nucleotide sequencing of all protein-coding regions and identified the germline mutations of the MEN 1 gene in two families with familial HPT. Patients with FIHPT have multiple abnormal parathyroid glands and are prone to both recurrent and persistent HPT. They frequently present with profound hypercalcemia, in contrast to patients with MEN-associated HPT or sporadic HPT. We recommend subtotal or total parathyroidectomy plus autotransplantation in patients with MEN-associated HPT and patients with FIHPT. Because parathyroid remains or supernumerary glands are often present in the thymus or perithymic tissue, we advocate routine bilateral dissection of the central zone with bilateral cervical thymectomy.

DNA↗
PubMed2001

Heightened expression of survivin in activated T lymphocytes from patients with multiple sclerosis.

The perpetuation of the inflammatory process in multiple sclerosis (MS) may arise from the failure to eliminate potentially pathogenic autoreactive lymphocytes by programmed cell death (apoptosis). Such impairment may be caused by multiple abnormalities of apoptosis regulatory proteins. In this study, we investigated the expression of survivin, a recently described cell cycle-regulated antiapoptosis protein, in lymphocytes from patients with active relapsing-remitting MS and appropriate controls. Survivin reactivity was detected in intrathecal lymphocytes from some MS patients, but not in resting peripheral lymphocytes. However, mitogen stimulation of resting lymphocytes induced survivin expression, which was significantly higher in stimulated intrathecal and peripheral T lymphocytes from MS patients when compared to controls. In contrast, cellular expression of the antiapoptosis protein Bcl-2 was relatively similar between MS patients and the control groups. Moreover, heightened survivin expression in MS patients correlated with T lymphocyte resistance to apoptosis, and was independent of cellular expression of the death receptor Fas. These findings suggest that upregulation of the antiapoptotic protein survivin in mitogen-stimulated T lymphocytes is a feature of multiple sclerosis.

Apoptosis↗
PubMed1996

A comparison of mechanisms underlying disturbances of bleeding caused by spontaneous dysfunctional uterine bleeding or hormonal contraception.

Recent research has not been able to demonstrate close endometrial morphological correlations with specific abnormalities of menstrual bleeding, but has pointed to an increasing number of molecular mechanisms that may be involved in the occurrence of certain forms of abnormal uterine bleeding. Ovulatory and anovulatory dysfunctional uterine bleeding (DUB) and progestogen-related breakthrough bleeding (BTB) are three conditions with quite different clinical characteristics. It is also probable that the local endometrial molecular mechanisms associated with these three menstrual disturbances are quite different. Ovulatory DUB is associated with a series of vascular and haemostatic disturbances that all appear to contribute to increased loss of blood and tissue fluid at menstruation. Anovulatory DUB is associated with obvious disturbances of endometrial histology, vascular morphology and fragility, with variable and increased blood flow. Progestogen-related BTB is associated with a multitude of morphological and functional endometrial changes that appear to relate predominantly to a patchy capillary origin for the bleeding. Many molecular and cellular changes have been observed in all three conditions. It is not yet known whether there is a single, but different, underlying mechanism responsible for these multiple abnormalities in each of the three clinical situations.

Anovulation↗
PubMed2004

Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer.

Dyskeratosis congenita (DC) is a severe, inherited, bone marrow failure syndrome, with associated cutaneous and noncutaneous abnormalities. DC patients also show signs of premature ageing and have an increased occurrence of cancer. DC can originate through: (1) mutations in DKC1, which result in X-linked recessive DC; (2) mutations in the RNA component of telomerase (TERC), which result in autosomal dominant DC (AD-DC); and (3) mutations in other, currently uncharacterized, genes, which result in autosomal recessive DC (AR-DC). As DKC1 encodes dyskerin, a protein component of small nucleolar ribonucleoprotein (snoRNP) particles, which are important in ribosomal RNA processing, DC was initially described as a disorder of defective ribosomal biogenesis. Subsequently, dyskerin and TERC were shown to closely associate with each other in the telomerase complex, and DC has since come to be regarded as a telomerase deficiency disorder characterised by shorter telomeres. These findings demonstrate the importance of telomerase in humans and highlight how its deficiency (through DKC1 and TERC mutations) results in multiple abnormalities including premature ageing, bone marrow failure and cancer. Identification of the gene(s) involved in AR-DC will help to define the pathophysiology of DC further, as well as expand our insights into telomere function, ageing and cancer.

Aging↗
PubMed1982

Hypertension in adult onset diabetes mellitus: abnormal renal hemodynamics and endogenous vasoregulatory factors.

We evaluated 10 adult onset diabetics who developed hypertension well after the onset of glucose intolerance. Systemic and renal hemodynamics, intravascular volume, the renin-angiotensin-aldosterone axis, and the renal kallikrein-kinin system were examined at extremes of sodium intake, and compared to results from matched normotensive and essential hypertensive subjects. On unrestricted sodium diet, the diabetics, compared to normotensives, had significantly decreased blood volume (p less than 0.01), and preservation of renal plasma and blood flow, but significantly elevated renal vascular resistance (p less than 0.05), decreased creatinine clearance (p less than 0.01), and decreased filtration fraction (p less than 0.01). On restricted sodium intake, diabetics, compared to normotensives, had reduced urinary kallikrein activity (p less than 0.01) and reduced ambulatory plasma renin activity (p less than 0.01). Essential hypertensives were similar to diabetics in that both had reduced intravascular volume, elevated renal vascular resistance, and reduced levels of stimulated urinary kallikrein and ambulatory renin activities, but plasma aldosterone concentrations were reduced in diabetics compared to both normotensives and essential hypertensives under all dietary conditions. The ratio urinary kallikrein activity/supine plasma renin activity in diabetics correlated with renal blood flow (p less than 0.05), and inversely with renal vascular resistance (p less than 0.05). We conclude that these hypertensive diabetics have multiple abnormalities in intrarenal hemodynamics that may be related, in part, to abnormal activities of the renal enzymes renin and kallikrein. The kallikrein defect may be an etiologic factor in their hypertension.

Aldosterone↗
PubMed1989

Local abnormalities of coagulation and fibrinolytic pathways that promote alveolar fibrin deposition in the lungs of baboons with diffuse alveolar damage.

Because alveolar fibrin is a prominent histologic feature of diffuse lung injury in baboons, we hypothesized that local abnormalities of pathways of fibrin turnover would favor fibrin deposition in the alveolar space. To test this hypothesis, procoagulant and fibrinolytic activities were characterized in serial bronchoalveolar lavage (BAL) of baboons with evolving diffuse alveolar damage (DAD) induced by exposure to 100% O2. BAL procoagulant activity, characterized mainly as the tissue factor-Factor VII complex, was markedly increased after induction of DAD. Extrinsic pathway inhibitor was likewise increased in BAL during evolving DAD but was insufficient to control coagulation. Urokinase-like fibrinolytic activity was usually detectable in baseline BAL but was undetectable after 7 d of O2. DAD BAL contained significantly increased plasminogen levels, plasmin inhibitor activity sufficient to neutralize all plasmin produced by BAL plasminogen activator found in control BAL and detectable plasminogen activator inhibitor-1. Antiplasmin activity was due, in part, to increased alpha 2-antiplasmin. These changes correlated with quantitatively increased alveolar fibrin deposition demonstrated by histologic and morphometric analyses. Multiple abnormalities of pathways of fibrin turnover occur concurrently in the alveolar compartment of the lungs of baboons with DAD, which collectively predispose to diffuse alveolar fibrin deposition.

Animals↗