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Biomedical subjects

S Nightingale

Publications and source records attributed to S Nightingale.

At least 37 records · Page 2Linked to original sources
PubMed1994

The prevalence of hepatitis B and C in an antenatal population of various ethnic origins.

A total of 3522 samples of serum, collected anonymously from women attending an antenatal clinic, was tested for hepatitis B surface antigen and antibody to hepatitis C. The prevalence of anti-HCV was low; only five confirmed positives were found (0.14%). The prevalence of hepatitis B overall was 0.56%, but was 1.04% in women from immigrant groups. Hepatitis B carriage is therefore four times more common than hepatitis C carriage in the antenatal population comprised of various ethnic origins. The patterns of infection in the two viruses are reversed, hepatitis B being more common in Asian, S.E. Asian and West Indian mothers and hepatitis C being more common in mothers of white Caucasian origin. Routine antenatal screening for anti-HCV is discussed.

Adolescent↗
PubMed1994

The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis.

Human T-cell leukemia virus type I (HTLV-1) causes T-cell leukemia and tropical spastic paraparesis (TSP) in a minority of infected people, whereas the majority remain healthy. No association between a particular HTLV-I sequence and disease manifestation has been found in previous studies. We studied here the sequence variability of the gene for the HTLV-I Tax protein, which is the dominant target antigen of the very strong cytotoxic T-lymphocyte response to the virus. In HTLV-I infection, the intraisolate nucleotide variability is much greater than the variability between isolates. The predicted protein sequence of Tax was significantly more variable in the healthy seropositive individuals' provirus than in those of the patients with TSP. Thus, tax sequence heterogeneity, rather than the presence of particular sequences, distinguishes healthy HTLV-I-seropositive individuals from patients with TSP.

Base Sequence↗
PubMed1994

Circulating anti-Tax cytotoxic T lymphocytes from human T-cell leukemia virus type I-infected people, with and without tropical spastic paraparesis, recognize multiple epitopes simultaneously.

CD8+ T cells were freshly isolated from a human T-cell leukemia virus type I (HTLV-I)-infected patient with tropical spastic paraparesis. These cells, which were specific for HTLV-I Tax, simultaneously recognized a minimum of five, and possibly as many as seven, distinct peptide epitopes within the protein. A further Tax epitope was recognized after a short period of culture without exogenous peptide stimulation. All but one of these epitopes were clustered in the N-terminal third of Tax, and one of the epitopes was clearly immunodominant on two separate occasions of testing. Recognition of the immunodominant epitope was restricted by human leukocyte antigen (HLA) B15, and recognition of all the others was by HLA A2. Similar patterns of cytotoxic T lymphocyte recognition of the HLA A2-restricted Tax peptides in two healthy HTLV-I-seropositive individuals, each of whom carried the HLA A2 allele, were observed.

Adult↗
PubMed1993

Antenatal survey for the seroprevalence of HTLV-1 infections in the West Midlands, England.

The sera of 3522 women who attended an antenatal clinic in Birmingham, England were tested anonymously for antibodies against HTLV-1. Samples from 5 women (0.14%) were positive, one serum showed indeterminate reactivity. Two of the women (0.06%) were born in the West Indies (of Afro-Caribbean ethnic origin), one (0.03%) in Africa (of African ethnic origin), and three (0.09%) were white Caucasian women born in the UK. Thus, HTLV-1 infection in pregnant women in the UK, though comparatively rare, is not negligible. As transmission of HTLV-1 to the newborn via breast milk has been observed and as seropositive mothers can be advised to refrain from breastfeeding or to treat their milk, the question of routine screening for HTLV-1 infection during antenatal care is discussed.

Adolescent↗
PubMed1993

Complete sequence conservation of the human T cell leukaemia virus type 1 tax gene within a family cluster showing different pathologies.

We have amplified, through PCR, the full-length tax gene of human T cell leukaemia virus type 1 (HTLV-1) derived from proviral DNA of peripheral blood lymphocytes of five first degree relatives of Afro-Caribbean origin. One patient (the father) had adult T cell leukaemia (ATL), one (the mother) tropical spastic paraparesis (TSP), and three (children) were healthy asymptomatic carriers. All five family members had identical tax nucleotide sequences as determined by direct sequencing of PCR products. This sequence was compared with tax gene sequences of an unrelated TSP patient of Afro-Caribbean origin, and of C8166 cells, and found to have one and seven nucleotide differences, respectively. At the amino acid level these three sequences differed from the HTLV-1 prototype Japanese strain (ATK-1). All sequence changes were clustered towards the 3' end of the gene. These data demonstrate the complete conservation of an HTLV-1 gene following, presumably, horizontal and vertical transmission of the virus. Clones of this gene showed more sequence variation within the TSP patient than the ATL patient, mostly consisting of point mutations; there was no conservation of mutations between the two individuals. These mutations occurred only in individual clones of the ATL patient whereas those of the TSP patient were found to be repeated in different clones. A tax-specific cytotoxic T lymphocyte response was observed in two asymptomatic carriers with low antibody titres, whereas none was detected in an individual with a high antibody level. No tax-specific sequence was identified which may have contributed to the apparently high degree of transmission from mother to children (three of five children tested) nor account for the differences between disease symptoms in the parents.

Adult↗
PubMed1992

Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis.

In human T cell lymphoma/leukemia virus (HTLV-1)-infected people with tropical spastic paraparesis (TSP), there are activated HTLV-1-specific cytotoxic T lymphocytes (CTL) in the circulation and lymphocytic infiltrates in spinal cord lesions that are rich in CD8+ T cells. These observations suggest a role for virus-specific CTL in the pathogenesis of TSP. We have examined the anti-HTLV-1 cytotoxic activity of freshly isolated CD8+ T cells from peripheral blood lymphocytes of eight subjects seropositive for HTLV-1. Four of five subjects with TSP had circulating activated anti-Tax CTL. However, two of three seropositive subjects without TSP also had activated anti-Tax CTL. These observations show that such activated CTL are not confined to patients with TSP and raise some uncertainty about their significance in the pathogenesis of the disease. In cultures of CD8+ T cells from two TSP subjects, we detected CTL with other HTLV-1 specificities, without exogenous antigenic stimulation. A CTL epitope in the middle region of Tax and one in the C terminus of Pol have been mapped at the peptide level and the HLA Class 1 molecules restricting their recognition have been defined.

Amino Acid Sequence↗
PubMed1991

Intermittent vertical supranuclear ophthalmoplegia and ataxia.

A 6-year-old girl is described with a history of episodes of severe ataxia precipitated by fever since the age of 11 months and in whom mental and physical development was otherwise normal. The ataxia was associated with a complete vertical supranuclear ophthalmoplegia and normal horizontal eye movements. After resolution of the attack she had no abnormal movement of her limbs or clinical evidence of ophthalmoplegia, though electro-oculograms showed a persistent mild deficit of vertical saccades. In between the attacks hyperglycinuria, an elevated plasma glycine level (687 mumol L(-1], and negative screening for organic aciduria suggest that she may have nonketotic hyperglycinaemia. To our knowledge, intermittent vertical supranuclear ophthalmoplegia and ataxia in a normally developing child has not been reported previously.

Cerebellar Ataxia↗
PubMed1991

Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy.

Increased flux through the polyol pathway mediated by the enzyme aldose reductase may be associated with the development of diabetic neuropathy. Fifty-four diabetic patients (median age 56 yr, range 25-65 yr) with chronic neuropathic symptoms were randomly allocated to placebo or aldose reductase inhibition (300 or 600 mg ponalrestat ICI 128436) groups for 24 wk. Patients with vibration perception thresholds (VPTs) greater than 35 V at the great toe or thermal difference thresholds (TTs) greater than 10 degrees C on the dorsum of the foot were excluded from the trial. No significant changes were observed in symptoms of pain, numbness, or paresthesia between ponalrestat and placebo groups, and there were no improvements in VPT or TT at several sites. Posterior tibial nerve conduction velocity changed from 35.3 +/- 4.9 m/s at baseline to 33.4 +/- 4.0 m/s at 24 wk (NS) with placebo compared with 37.6 +/- 5.6 vs. 37.2 +/- 8.7 m/s (NS) with 300 mg ponalrestat and 34.5 +/- 6.1 vs. 36.2 +/- 6.8 m/s (NS) with 600 mg ponalrestat. Further studies are indicated with intervention at an earlier stage in the evolution of neuropathy and for longer periods.

Aldehyde Reductase↗
PubMed1990

Fibrinolytic activity after subarachnoid haemorrhage and the effect of tranexamic acid.

Seventy-four patients with recent subarachnoid haemorrhage were randomly allocated to placebo or tranexamic acid treatment. Fibrinolytic activity in the blood and cerebrospinal fluid was assessed before treatment, one week later and two weeks later. The natural history of fibrinolysis following subarachnoid haemorrhage was obtained from analysis of the placebo group. Following subarachnoid haemorrhage, fibrin degradation products and plasminogen activity in the cerebrospinal fluid were elevated. Subsequently, fibrin degradation products in the cerebrospinal fluid fell progressively over the following 2 weeks. Changes in cerebrospinal fluid plasminogen activity correlated with those of blood plasminogen activity. Complications such as rebleeding, hydrocephalus or cerebral thrombosis could not be predicted from analysis of fibrinolytic activity. Tranexamic acid treatment resulted in a reduction in cerebrospinal fluid and blood plasminogen activity. The relevance of fibrinolysis in cerebrospinal fluid and blood to the management of subarachnoid haemorrhage is discussed.

Antifibrinolytic Agents↗
PubMed1990

Prolonged aldose reductase inhibition in chronic peripheral diabetic neuropathy: effects on microangiopathy.

A 2-year randomized placebo-controlled double-blind trial of 250 mg day-1 of the aldose reductase inhibitor Sorbinil in severe symptomatic chronic peripheral neuropathy was performed in 21 diabetic patients. Due to adverse reactions 8 patients completed the trial on Sorbinil and 6 patients on placebo. Despite differences in baseline neurophysiological parameters, duration of diabetes, and presence of retinopathy between the placebo and treatment groups, there were no initial differences in in vitro platelet aggregation, albumin excretion rate (AER) or muscle capillary basement membrane thickness. After 2 years the median deterioration in AER in the placebo group was 18.4 micrograms min-1 (range 2.6-64.8 micrograms min-1). This deterioration was significant (p less than 0.03). The change in AER in the Sorbinil group was +1.25 (-10.7 to +20.4) micrograms min-1, an insignificant change. In vitro platelet responsiveness to collagen and adenosine diphosphate (ADP) increased in the placebo group (median change max% collagen + 8 (+2 to +30)%; ADP +4.5 (0 to +20)% compared with a fall in the Sorbinil treated patients (median change; collagen -17.5 (-2 to -40)%, p less than 0.05; ADP, -4 (0 to -25)%, p less than 0.05). Muscle capillary basement membrane thickness was measured in only 3 patients in each group and did not alter significantly during the trial. All 12 neurophysiological measurements showed no significant changes between the treatment and placebo groups. The data suggest that aldose reductase inhibition has effects on platelet reactivity and microalbuminuria.

Aldehyde Reductase↗
PubMed1990

Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis.

The fatty acid profiles of phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) of the red blood cells of 30 patients with mild inactive multiple sclerosis (MS) and 30 healthy controls were studied by gas chromatography. The groups were well matched for factors likely to influence tissue lipid levels, including diet. The MS patients showed a significant reduction in PE eicosapentaenoic acid (p = 0.009) especially in women, and an increase in both PE dihomo-gamma-linolenic acid (p = 0.004) and PC stearic acid (p = 0.04). No reduction in linoleic acid was observed in either the PC or PE fractions of the MS subjects. A similar study of the fatty acid profile in adipose tissue in 26 MS and 35 healthy controls found no detectable eicosapentaenoic acid in either group. However, whereas docosahexaenoic acid was not detectable in any MS patient, 40% of the controls had measurable levels varying from to 0.1 to 0.3% of total estimated fatty acid (p = 0.0003). No reduction in linoleic acid in MS subjects was observed. Supplementation with oral fish body oil demonstrated that n-3 fatty acids were incorporated into red blood cells over 5 weeks and this occurred equally in MS and controls. The effects of oral supplementation on adipose tissue were studied after 1 and 2 years. Whereas many fatty acids such as linoleic acid were raised at 1 year, but did not rise subsequently, eicosapentaenoic acid and docosahexaenoic acid continued to rise through the 2-year period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1990

Sequence variants of human T-cell lymphotropic virus type I from patients with tropical spastic paraparesis and adult T-cell leukemia do not distinguish neurological from leukemic isolates.

We have amplified and sequenced DNA in the envelope (env) and long terminal repeat (LTR) regions of human T-cell lymphotropic virus type I (HTLV-I) proviruses from the peripheral blood of 10 HTLV-I-seropositive patients with tropical spastic paraparesis (TSP) and two patients with adult T-cell leukemia. The aim was to examine variation in these regions and to test the hypothesis that the sequences of leukemogenic HTLV-I isolates differ from those causing the neurological disease TSP. In 5 of the 12 HTLV-I-seropositive patients, more than one HTLV-I sequence variant was identified in the same individual. No two individuals shared identical sequences in either env or LTR U3. Sequence variations were found at 73 positions in 1,416 bases amplified in env. Sequence variability was found throughout the LTR-U3 region, including the sequences of two transcriptional enhancers. Several nucleotide changes common to both Caribbean and Japanese HTLV-I isolates allowed us to identify a consensus sequence that differs from the HTLV-I prototype sequence (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida, Proc. Natl. Acad. Sci. USA 80:3618-3622, 1983). No sequence in the env or LTR U3 region was found to be characteristic of isolates from TSP patients. Although each isolate was distinct at the nucleotide level, the predicted protein sequence of HTLV-I env is less variable than that of human immunodeficiency virus env, suggesting that these lymphotropic retroviruses use different strategies to evade host immune responses.

Adult↗
PubMed1990

Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies.

Multiple sclerosis (MS) is very uncommon among ethnic Asians in the Indian subcontinent, among Asians and Africans resident in the New Commonwealth countries of Africa and in the West Indies. It is also very uncommon among those who have migrated to England from those countries. In contrast, the children born in the United Kingdom of Asian, African and West Indian immigrants have, in the age groups available for study, a high prevalence of MS of a similar order to that occurring in the general population of England.

Adolescent↗
PubMed1990

Impact of microangiopathy on chronic symptomatic peripheral neuropathy.

The role of microvascular disease in the aetiology of diabetic peripheral neuropathy remains controversial. Muscle capillary basement membrane thickening (MCBMT) and increased albumin excretion rates (AER) are features of generalized diabetic microangiopathy and may relate to the severity of neuropathy. We have studied 19 patients with neuropathy of greater than 12 months duration and assessed relationships between the severity of neuropathy and MCBMT, AER, presence of retinopathy, age and duration of diabetes. Nine patients had retinopathy and 10 did not. The two groups of patients were well matched for age, type of diabetes and HbA1% but diabetic patients with retinopathy had significantly longer duration of diabetes (median duration 22 yr, range 3-42 yr compared with patients without retinopathy (6 yr range 1-20 yr p less than 0.05). The group with retinopathy had significantly greater median MCBMT 3,077 A (range 741-10,732 A) than their age matched non-diabetic controls 2,256 A (1,290-4,406 A p less than 0.02) or the 10 diabetic patients without retinopathy 1,599 A (805-5,152 A). The patients with retinopathy also had greater median AER 88 micrograms/min (range 8-200 micrograms/min) compared with patients without retinopathy 8 micrograms/min (2-63 micrograms/min p less than 0.05), and had significantly more severe neuropathic features on a 12 point neurophysiological ranking scale (p less than 0.05). This study showed an association between retinopathy and severity of neuropathy but there were no associations between severity of neuropathy or AER with MCBMT. Severe chronic peripheral neuropathy is associated with microangiopathic complications.

Albuminuria↗
PubMed1989

Epidemiology of human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) infections in a subpopulation of Afro-Caribbean origin in England.

Epidemiological studies on neurological diseases in residents of Afro-Caribbean origin in the West Midlands region of England have identified eight patients with tropical spastic paraparesis (TSP), all of whom were found to be infected with human T-cell leukaemia/lymphoma virus type 1 (HTLV-1). The husband of one of the patients with TSP was also infected with HTLV-1 and had a T-cell lymphoma. In addition, six asymptomatic HTLV-1-infected first-degree relatives of the TSP patients have been found. By anonymous testing of over 700 sera obtained from individuals of Afro-Caribbean, African, or Asian ethnic origin, seven HTLV-1-infected individuals were detected, who were all immigrants from the Caribbean. Overall, these numbers yielded a seroprevalence of HTLV-1 infections of 3.4% among the immigrant population of Afro-Caribbean origin, which is comparable with the prevalence of HTLV-1 in Jamaica in an equivalent age and sex cohort. Sera were tested for HTLV-1 antibody by means of three different procedures: passive particle agglutination test (Serodia), indirect enzyme-labeled immunosorbent assay (ELISA; Dupont), and indirect immunofluorescence test (in-house, using HTLV-1-infected MT2 cells). The results of all three tests correlated very well with each other. HTLV-1 antibody titres in TSP patients were on the whole significantly higher than those of asymptomatic carriers, but some of the apparently healthy first-degree relatives and one anonymously tested individual had titres as high as most of the TSP patients.

Black or African American↗