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Biomedical subjects

V Adams

Publications and source records attributed to V Adams.

At least 19 recordsLinked to original sources

COX-1 and COX-2 expression in feline oral squamous cell carcinoma.

This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (< or = 1%) of neoplastic cells and its intensity was usually mild to moderate. In contrast, all neoplastic tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.

Animals↗

Serotyping and genotyping of HIV-1 infection in residents of Khayelitsha, Cape Town, South Africa.

It is estimated that between 5.5 and 6.1 million people are infected with HIV/acquired immunodeficiency syndrome (AIDS) in South Africa, with subtype C responsible for the majority of these infections. The Khayelitsha suburb of Cape Town has one of the highest HIV prevalence rates in South Africa. Overcrowding combined with unemployment and crime in parts of the area perpetuates high-risk sexual behavior, which increases exposure to infection by HIV. Against this background, the objective of this study was to characterize HIV-1 in residents confirmed to be seropositive. Serotyping was performed through a competitive enzyme-linked immunosorbent assay (cPEIA). Genotyping methods included RNA isolation followed by RT-PCR and sequencing of the gag p24, env gp41 immunodominant region (IDR), and env gp120 V3 genome regions of HIV-1. With the exception of a possible C/D recombinant strain, all HIV-1 strains were characterized as HIV-1 group M subtype C. One individual was shown to harbor multiple strains of HIV-1 subtype C. In Southern Africa, the focus has been to develop a subtype C candidate vaccine, as this is the major subtype found in this geographical area. Therefore, the spread of HIV-1 and its recombinant strains needs to be monitored closely.

Adult↗

Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell carcinoma--a case series of five dogs.

Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.

Animals↗

Association of spinal cord compression seen on magnetic resonance imaging with clinical outcome in 67 dogs with thoracolumbar intervertebral disc extrusion.

OBJECTIVES: To determine whether there is an association between the degree of transverse spinal cord compression detected by magnetic resonance imaging following thoracolumbar Hansen type 1 intervertebral disc disease in dogs and their presenting and postsurgical neurological status. METHODS: Medical records of 67 dogs with surgically confirmed Hansen type 1 intervertebral disc disease (2000 to 2004) were reviewed to obtain the rate of onset of disease, duration of clinical signs and presurgical and postsurgical neurological grade. Percentage of spinal cord compression was determined on transverse T2-weighted magnetic resonance images. Linear regression was used to examine the association between spinal cord compression and each of the above variables. Chi-squared tests were used to examine associations among postsurgical outcome and presurgical variables. RESULTS: Eighty-five per cent (57 of 67) of dogs were chondrodystrophoid. Mean spinal cord compression was 53 per cent (sd=219.7, range 14.3 to 84.9 per cent). There was no association between the degree of spinal cord compression and the neurological grade at presentation, rate of onset of disease, duration of clinical signs or postsurgical outcome, with no difference between chondrodystrophoid and non-chondrodystrophoid dogs. CLINICAL SIGNIFICANCE: The degree of spinal cord compression documented with magnetic resonance imaging in dogs with thoracolumbar Hansen type 1 intervertebral disc disease was not associated with the severity of neurological signs and was not a prognostic indicator in this study.

Animals↗

The effects of halothane and isoflurane on cardiovascular function in laterally recumbent horses.

BACKGROUND: Experimental studies in adult horses have shown that general anaesthesia maintained with isoflurane is associated with less depression of cardiovascular function compared with halothane anaesthesia. Adverse effects of intermittent positive-pressure ventilation (IPPV) have also been demonstrated. Nevertheless, the haemodynamic effects of these agents and the effects of differing modes of ventilation have not been assessed during clinical anaesthesia in horses undergoing surgery. METHODS: The haemodynamic effects of isoflurane or halothane anaesthesia during spontaneous or IPPV were studied non-invasively in 32 laterally recumbent horses undergoing elective surgery. Indices of cardiac function and measurements of femoral arterial blood flow and resistance were recorded using transoesophageal and transcutaneous Doppler echocardiography, respectively. Arterial pressure was measured directly using a facial artery catheter. RESULTS: Cardiac index (CI) was significantly higher during isoflurane anaesthesia than during halothane anaesthesia and was also higher during spontaneous ventilation with isoflurane. CI decreased significantly over time and an inverse relationship was observed between CI and mean arterial pressure (MAP). Horses with higher MAP had a significantly lower CI. During isoflurane anaesthesia, femoral arterial blood flow was significantly higher in both pelvic limbs compared with halothane anaesthesia, and flow in the lower limb was significantly higher during spontaneous ventilation than during IPPV. No significant change in femoral blood flow was observed over time. CONCLUSION: The effects of anaesthetics and mode of ventilation on cardiovascular function recorded under surgical conditions in horses are similar to those reported under experimental conditions. However, in contrast with previous experimental studies, CI progressively decreased over time regardless of agent used or mode of ventilation employed.

Anesthesia, Inhalation↗

Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders.

In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn's disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg). This paper provides an overview of relevant work in each of these fields of medicine (though with emphasis on the allergic disorders), and concludes that the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are "old friends", because of their continuous presence throughout mammalian evolution. These organisms, which include saprophytic mycobacteria, helminths and lactobacilli, are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. Polymorphisms of components of the innate immune system such as TLR2 and NOD2 appear to define subsets of the population that will develop immunoregulatory disorders when living in the modern environment. A further role of the "old friends" and of the Treg that they induce might be to maintain the levels of regulatory IL-10 secreting macrophages and antigen-presenting cells, which are depleted in asthma and Crohn's disease. These concepts are leading to novel therapies based on harmless organisms or their components. Phase I/II clinical trials have yielded some statistically significant results, and phase II trials are in progress.

Adjuvants, Immunologic↗

Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase.

BACKGROUND: In stable coronary artery disease (CAD), exercise training has well-documented positive effects on arterial endothelial function. NO derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery (LIMA) of patients with stable CAD. METHODS AND RESULTS: In 17 training patients (T) and 18 control patients (C), endothelium-dependent vasodilation and average peak flow velocity (APV) in response to acetylcholine were measured invasively at study beginning and after 4 weeks in the LIMA. In LIMA tissue sampled during bypass surgery, eNOS expression and content of pospho-eNOS-Ser1177, Akt, and phospho-Akt were determined by Western blot and quantitative reverse transcriptase-polymerase chain reaction. After exercise training, LIMA APV in response to acetylcholine was increased by 56+/-8% (from +48+/-8% at beginning to +104+/-11% after 4 weeks, P<0.001). Patients in T had a 2-fold higher eNOS protein expression (T 1.0+/-0.7 versus C 0.5+/-0.3 arbitrary units, P<0.05) and 4-fold higher eNOS Ser1177-phosphorylation levels in LIMA-endothelium (1.2+/-0.9 versus 0.3+/-0.2 arbitrary units, P<0.01). A linear correlation was confirmed between Akt phosphorylation and phospho-eNOS levels (R=0.80, P<0.05) and between phospho-eNOS and Delta APV (R=0.59, P<0.05). CONCLUSIONS: Exercise training in stable CAD leads to an improved agonist-mediated endothelium-dependent vasodilatory capacity. The change in acetylcholine-induced vasodilatation was closely related to a shear stress-induced/Akt-dependent phosphorylation of eNOS on Ser1177.

Acetylcholine↗

HHV-8 DNA sequences in the peripheral blood and skin lesions of an HIV-negative patient with multiple eruptive dermatofibromas: implications for the detection of HHV-8 as a diagnostic marker for Kaposi's sarcoma.

BACKGROUND: Multiple eruptive dermatofibroma (MEDF) is a rare disorder seen in immunocompromised patients, simulating Kaposi's sarcoma (KS). Whereas KS is strongly associated with human herpesvirus 8 (HHV-8), the virus has never been detected in MEDF until now. OBJECTIVE: To present a patient with MEDF who showed no signs of immunodeficiency but was seropositive for HHV-8 antibodies and demonstrated HHV-8 DNA both in the peripheral blood and lesional skin of MEDF. METHODS: Clinical, histological and serological investigations were performed as well as polymerase chain reaction (PCR) studies and in situ hybridization (ISH). RESULTS: A 35-year-old white man with suspected KS was referred for evaluation of multiple pigmented nodules and patches. Biopsies revealed features of dermatofibroma, superficial fibrosing dermatitis and scar. One of the nodular lesions harbored HHV-8 DNA sequences. A faint amplification product was detected in the superficial fibrosing dermatitis lesion, while no HHV-8 sequences were found in normal skin and scar. Whole-blood samples and serum were positive for HHV-8. None of the skin lesions shown to harbor HHV-8 DNA sequences by nested PCR displayed a signal for HHV-8 RNA by ISH. Repetitive peripheral blood examinations did not reveal any serum antibodies against or antigens of HIV. Serum antibodies against the HHV-8 capsid antigen orf 65.2 were detected. CONCLUSION: Results of PCR studies and ISH indicate that the presence of HHV-8 in the lesional tissue was probably blood-borne due to viremia and not due to viral replication in tumor cells. The presence of HHV-8 is not fully restricted to KS. The differential diagnosis of KS and its simulators should be based on an integrative analysis of all available clinicopathological and molecular data and should not rely exclusively or predominantly on the presence or absence of HHV-8.

Adult↗

The clostridial mobilisable transposons.

Mobilisable transposons are transposable genetic elements that also encode mobilisation functions but are not in themselves conjugative. They rely on coresident conjugative elements to facilitate their transfer to recipient cells. Clostridial mobilisable transposons include Tn4451 and Tn4452 from Clostridium perfringens, and Tn4453a and Tn4453b from Clostridium difficile, all of which are closely related, and Tn5398 from C. difficile. The Tn4451 group of elements encodes resistance to chloramphenicol and is unusual in that transposition is dependent upon a large resolvase protein rather than a more conventional transposase or integrase. This group of elements also encodes the mobilisation protein TnpZ that, by acting at the RS(A) or oriT site located on the transposon, and in the presence of a coresident conjugative element, promotes the movement of the nonreplicating circular intermediate and of plasmids on which the transposon resides. The erythromycin resistance element Tn5398 is unique in that it encodes no readily identifiable transposition or mobilisation proteins. However, the element is still capable of intraspecific transfer between C. difficile isolates, by an unknown mechanism. The detailed analysis of these mobilisable clostridial elements provides evidence that the evolution and dissemination of antibiotic resistance genes is a complex process that may involve the interaction of genetic elements with very different properties.

Clostridium↗

Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.

The lysosomal storage disorder, mucopolysaccharidosis type I (MPS I), is caused by a deficiency of the enzyme alpha-L-iduronidase, which is involved in the breakdown of dermatan and heparan sulphates. There are three clinical phenotypes, ranging from the Hurler form characterised by skeletal abnormalities, hepatosplenomegaly and severe mental retardation, to the milder Scheie phenotype where there is aortic valve disease, corneal clouding, limited skeletal problems, but no mental retardation. In this study, 85 MPS I families (73 Hurler, 5 Hurler/Scheie, 7 Scheie) were screened for 9 known mutations (Q70X, A75T, 474-2a>g, L218P, A327P, W402X, P533R, R89Q, 678-7g>a). W402X was the most frequent mutation in our population (45.3%) and Q70X was the second most frequent (15.9%). In 30 families, either one or both of the mutations were not identified, which accounted for 25.9% of the total alleles. Therefore, all 14 exons of the alpha-L-iduronidase gene were screened in these patients and 23 different sequence changes were found, 17 of which were previously unknown. The novel sequence changes include 4 deletions (153delC, 628del5, 740delC, 747delG), 5 nonsense mutations (Q60X, Y167X, Q400X, R619X, R628X), 6 missense mutations (C205Y, G208V, H240R, A319V, P496R, S633L), a splice site mutation (IVS12+5g>a), and a rare polymorphism (A591T). The polymorphism and novel missense mutations were transiently expressed in COS-7 cells and all of them except the polymorphism showed complete loss of enzyme activity. In total, 165 of the 170 mutant alleles were identified in this study and despite the high frequency of W402X and Q70X, the identification of many novel mutations unique to individual families further highlights the genetic heterogeneity of MPS I.

Animals↗

Differentially expressed genes in L6 rat skeletal muscle myoblasts after incubation with inflammatory cytokines.

OBJECTIVE: The mechanism underlying exercise intolerance in chronic heart failure is still unclear. An increased concentration of inflammatory cytokines could be detected in the serum of patients with chronic heart failure (CHF) exhibiting a correlation with the severity of the disease. The variety of molecular alterations triggered by these cytokines in the skeletal muscle is almost unknown. The study was designed to analyze the differential gene expression in skeletal muscle myoblasts after stimulation with inflammatory cytokines. METHODS: L6 rat skeletal muscle myoblasts were incubated for 24 h with a combination of IL-1beta/IFN-gamma and the differential gene expression profile was determined by a PCR-based subtractive hybridization method. RESULTS: Out of 173 picked clones 141 different sequences could be identified. By comparison with Genebank, the identity of 73 genes (51.7%) could be confirmed, whereas the rest did not show a homology to any known gene. Some of the identified genes are known to be altered in patients with CHF. CONCLUSION: In summary, the results of this study provide information about changes in gene expression after exposure of skeletal muscle cells to inflammatory cytokines. This information may yield a new gene pool, worthwhile to be analyzed in skeletal muscle of patients with chronic heart failure.

Animals↗

Apoptosis in skeletal muscle.

Apoptosis is a physiological, conserved program of cellular suicide, characterized by nuclear condensation, DNA-fragmentation and release of mitochondrial cytochrome c into the cytoplasm. The apoptotic program is executed by a cascade of highly specific caspases. The occurrence and significance of apoptosis in multinucleated, differentiated cells, like skeletal muscle cells is discussed controversy in the current literature. In this review we will summarize the knowledge concerning the occurrence of apoptosis in certain diseases and the regulation of apoptosis in skeletal muscle.

Animals↗

Striatal dopaminergic and serotonergic markers in human heroin users.

To establish whether chronic opiate exposure might impair brain dopaminergic or serotonergic function in humans, we assessed biochemical indices of monoaminergic neurotransmitter activity and integrity in post mortem striatum of nine chronic heroin users and 14 control subjects. Striatal levels of the vesicular monoamine transporter were normal, suggesting that the density of dopamine nerve terminals is not reduced in heroin users. In nucleus accumbens, levels of tyrosine hydroxylase protein (-25%) and those of the dopamine metabolite homovanillic acid (-33%) were reduced significantly together with a trend for decreased dopamine (-32%) concentration. These changes could reflect either a compensatory downregulation of dopamine biosynthesis in response to prolonged dopaminergic stimulation caused by heroin, or reduced axoplasmic transport of tyrosine hydroxylase. Striatal levels of serotonin were either normal or elevated whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were decreased by 27-38%. Our data suggest that chronic heroin exposure might produce a modest reduction in dopaminergic and serotonergic activity that could affect motivational state and impulse control, respectively.

Adult↗

Venous air embolism in homicidal blunt impact head trauma. Case reports.

From 1992 through 1997, there were 41 deaths by homicidal blunt impact head trauma in Hillsborough County, Florida. Twenty-one cases were excluded from the study because of putrefaction or survival beyond the emergency department doors, leaving 20 cases for the study. One of the 15 nonputrefied victims found dead at the scene and 1 of the 5 victims pronounced dead in the emergency department had definite venous air embolism. Victim 1 was found dead, bludgeoned with a concrete block, and had open vault and comminuted basilar skull fractures. The dura forming the right sigmoid sinus at the jugular foramen was lacerated. A preautopsy chest radiograph and examination under water documented gas in the pulmonary artery and right ventricle. Victim 2 was bludgeoned with a steel stake and was pronounced dead on arrival in the emergency department. He had open comminuted vault fractures, a transverse basilar skull fracture, and lacerations of the brain. Direct examination and preautopsy chest radiography revealed air in the right side of the heart. A third victim, with basilar fractures, had a small gas bubble in the pulmonary artery not detected by the case pathologist. A fourth victim, with a basilar skull fracture, had an unusual radiographic finding that was thought to be air in the posteromedial aspect of the lower lobe of the left lung but could not be excluded as an air embolus. Optimal postmortem documentation of venous air embolism includes the demonstration of the embolus and the site of air ingress. This study demonstrates that venous air embolism occurs in some victims of homicidal bludgeoning and suggests that when significant, it is easily demonstrated in the absence of putrefactive gas formation. The presence of venous air embolism can serve as evidence that a victim was alive and breathing at the time of the infliction of head wounds. In the belief that venous air embolism might be underdiagnosed in many medical examiner offices, the authors have sought to bring attention to the entity by publishing their experience with it in cases of bludgeoning.

Adult↗

Increased expression of human herpesvirus 7 in lymphoid organs of AIDS patients.

BACKGROUND: Human herpesvirus 7 (HHV-7) interferes reciprocally with the human immunodeficiency virus (HIV) in CD4 T lymphocytes, as infection with HIV results in a down modulation of the CD4 molecule and inhibition of replication of HHV-7, and vice versa. Correlations between HHV-7 and HIV at the organ level have not been studied in detail. OBJECTIVE: To study the presence and cellular distribution of HHV-7 in lymphoid organs, i.e. lymph nodes (LNs) and spleen in AIDS patients and HIV-seronegative individuals. STUDY DESIGN: Cross-sectional study. The detection of HHV-7 specific antigen pp85, the 85 kDa encoded tegument phosphoprotein by U14 gene, was performed by immunohistochemistry (IHC) with a well characterized monoclonal antibody (mAb 5E1) to pp85. Nested polymerase chain reaction (PCR) was applied to detect HHV-7 specific DNA sequences. RESULTS: Cells infected with HHV-7 were detected in five of seven LNs from AIDS patients and in one of five LNs from HIV-seronegative patients. The infected cells were mainly macrophages. In samples from HIV-seropositive patients, a significantly higher number of HHV-7 infected cells could be observed than in specimens from HIV-seronegative patients. Neither the antigen nor DNA sequences of HHV-7 could be detected in spleen tissue from HIV-seronegative and AIDS patients. CONCLUSIONS: The data indicate that HHV-7 undergoes a higher extent of reactivation from latency and/or of replication under immunosuppression due to HIV-infection, similar to the other beta-herpesviruses HHV-6 and human cytomegalovirus (HCMV). The data further suggest that LNs, but not the spleen, may be a site of latency and consequently of reactivation of HHV-7 in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Dopamine D1 receptor protein is elevated in nucleus accumbens of human, chronic methamphetamine users.

Animal data have long suggested that an adaptive upregulation of nucleus accumbens dopamine D1 receptor function might underlie part of the dependency on drugs of abuse. We measured by quantitative immunoblotting protein levels of dopamine D1 and, for comparison, D2 receptors in brain of chronic users of methamphetamine, cocaine, and heroin. As compared with the controls, brain dopamine D1 receptor concentrations were selectively increased (by 44%) in the nucleus accumbens of the methamphetamine users, whereas a trend was observed in this brain area for reduced protein levels of the dopamine D2 receptor in all three drug groups (-25 to -37%; P < 0.05 for heroin group only). Our data support the hypothesis that aspects of the drug-dependent state in human methamphetamine users might be related to increased dopamine D1 receptor function in limbic brain.

Adult↗

The human nucleus accumbens is highly susceptible to G protein down-regulation by methamphetamine and heroin.

Although the nucleus accumbens is assumed to be a critical brain "pleasure center," its function in humans is unknown. As animal data suggest that a unique feature of this small brain area is its high sensitivity to down-regulation of an inhibitory G protein by drugs of abuse, we compared G protein levels in postmortem nucleus accumbens with those in seven other brain regions of chronic users of cocaine, methamphetamine, and heroin, and of matched controls. Biochemical changes were restricted to the nucleus accumbens in which concentrations of G(alpha)1 and/or G(alpha)2 were reduced by 32-49% in the methamphetamine and heroin users. This selective responsiveness to these abused drugs implies a special role for the human nucleus accumbens in mechanisms of drug reinforcement and suggests that some features of the drug-dependent state (e.g., tolerance) might be related to inhibition of G(alpha)1-linked receptor activity.

Adult↗