Biomedical subjects
A Marshall
Publications and source records attributed to A Marshall.
Clinical features of early onset, familial Alzheimer's disease linked to chromosome 14.
Early onset familial Alzheimer's disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the beta-amyloid precursor protein (beta APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with beta APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val-->Ile) or a valine to glycine (Val-->Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the beta APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the beta APP717 Val-->Ile and beta APP717 Val-->Gly encoded families that have been previously described.(ABSTRACT TRUNCATED AT 250 WORDS)
Sialosyl-Tn antigen: initial report of a new marker of malignant progression in long-standing ulcerative colitis.
BACKGROUND & AIMS: Expression of the mucin-associated carbohydrate antigen sialosyl-Tn (STn) correlates with malignant transformation in sporadic colonic neoplasms. The aim of this study was to analyze STn antigen expression in patients with long-standing ulcerative colitis (UC). METHODS: STn antigen was assessed by immunohistochemistry in archival tissues. Study A was a retrospective chronological case-control study. Serial surveillance colonoscopic biopsy specimens without inflammation or dysplasia were analyzed in 7 patients who developed colon cancer and in 8 controls who did not develop colon cancer. Study B analyzed the anatomic distribution of STn expression in 17 cancer-bearing (case) and 6 cancer-free (control) colectomy specimens from patients with UC. In some colectomy specimens, STn was compared with aneuploidy, which was determined by flow cytometry. RESULTS: In study A, among the 7 patients with UC who developed cancer, 6 patients (86%) expressed STn in at least one prior nondysplastic surveillance biopsy specimen from the same site. Only 3 of 8 control patients (38%) expressed STn. In study B, STn was expressed in 40 of 82 specimens (49%) from cancer-bearing colons but only 8 of 62 specimens (13%) from cancer-free colons. STn was expressed in most aneuploid areas but was also found in diploid, nondysplastic mucosa. CONCLUSIONS: STn antigen seems to be a promising marker of cancer risk in patients with UC.
Osteopenia, neurological dysfunction, and the development of Charcot neuroarthropathy.
OBJECTIVE: To determine factors that might be associated with the development of Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS: This cross-sectional prevalence study examined neurological function and bone density in matched groups of neuropathic diabetic patients with and without radiological evidence of Charcot neuroarthropathy. RESULTS: Patients with Charcot neuroarthropathy had a global impairment of neurological function that was significantly greater than that of otherwise matched non-Charcot neuropathic patients. All 17 Charcot patients had evidence of autonomic neuropathy compared with 10 of the control subjects (P = 0.03). The Charcot patients had evidence of reduced bone density in the lower limbs compared with the neuropathic control subjects (P = 0.009), but relatively preserved bone density in the spine (P = 0.4 vs. control subjects). CONCLUSIONS: We conclude that minor trauma in diabetic patients with peripheral neuropathy might result in a fracture in those with a reduced bone density and thus trigger the development of Charcot neuroarthropathy.
Magnetization scaling on thick YBa2Cu3O7-x single crystals.
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Synthesis and secretion of an estrus stage-specific protein by rat uterus.
A specific protein with an estimated molecular weight of 260 kDa was found to be synthesized and secreted into the incubation medium by rat uterus only during the estrus stage of the cycle. This secreted uterine protein was designated as estrus stage-specific protein (ESP). ESP was not produced by pregnant, lactating or immature pup rat uteri. Estradiol administered to ovariectomized rats induced production of ESP which was blocked by the antiestrogen, ICI 182, 780. The present results show that the synthesis and secretion of ESP is regulated by estradiol and this protein maybe involved in blastocyst implantation.
Understanding patterns of immunoglobulin gene rearrangements.
When immunoglobulin (Ig) gene rearrangements are analyzed, several patterns emerge. The rearrangements at the various loci generally appear in a specific temporal order. In addition, within a given locus the frequency of rearrangement of the various gene segments is not equal but is skewed towards preferential rearrangement of particular gene segments. Understanding the reasons for these patterns will shed light on the mechanism of recombination, the regulation of rearrangement, and the relationship between Ig gene rearrangement and B cell development. In this review, we discuss evidence that the observed patterns of Ig gene rearrangement are due to a combination of factors including the recombination signal sequences, sequences in the coding termini, the accessibility of genetic elements to V(D)J recombinase, and cellular selection.
Differential effect of estrogen on the production of cyclin B1, cdc2 p34 and c-fos protein in rat uterus.
The uterine content of c-fos protein, cyclin B1 (cell cycle protein) and cdc2 p34(cyclin-dependent kinase) in immature and mature rats was determined using the enhanced chemiluminescence(ECL) western blot method. Cyclin B1 was found predominantly in immature rat uterus and cdc2 p34 only in mature rat uterus. Several isoforms of c-fos oncogene protein were present in both mature and immature rat uteri. An additional immunoreactive c-fos protein with an estimated molecular weight of 28 kDa was found in mature rat uterus and was missing in immature uterus. Uteri from ovariectomized rats treated with estrogen and/or ICI 182,780, an antiestrogen, were analyzed by ECL western blot. cdc2 p34 and the c-fos 28 kDa protein were found in estradiol-treated rat uteri and were not detected in uteri of control and ICI 182,780-treated animals; whereas Cyclin B1 was absent in uteri from control and estradiol-treated ovariectomized animals. ICI 182,780 administered to estradiol-treated ovariectomized rats blocked the induction of cdc2 p34 and the c-fos 28 kDa protein in the uterus. The present results show that the production of the cell cycle factors, cyclin B1, cdc2 p34 and c-fos, during rat uterine growth are under different regulatory controls. cdc2 p34 and c-fos 28 kDa protein are under the control of estradiol; whereas cyclin B1 and the majority of the immunoreactive isoforms of c-fos are not influenced by this hormone.
Development of B lymphocytes from lymphoid committed and uncommitted progenitors.
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Contrasting effects of Mycoplasma fermentans and M. felis on the viability and chemiluminescence response of human polymorphonuclear leukocytes.
Trypan blue exclusion was used to estimate the viability of human polymorphonuclear leukocytes (PMNL) in the presence of Mycoplasma felis and two strains of M. fermentans (PG18 and incognitus). The competence of PMNL to mount a respiratory burst when challenged with the mycoplasmas was also monitored by luminol-dependent chemiluminescence (CL). Both un-opsonised and non-immune human serum opsonised M. felis cells had little effect on PMNL viability. In contrast, PMNL viability was reduced markedly by un-opsonised cells of M. fermentans strain incognitus and, to a lesser extent, strain PG18, and opsonisation of these mycoplasmas further enhanced killing. Death of PMNL in the presence of M. fermentans was not associated with the autonomous production of active oxygen species during the respiratory burst as M. felis induced a high CL response from PMNL, whereas that induced by M. fermentans strain incognitus was significantly lower. M. fermentans may invade mammalian cells and it is suggested that the mechanism of PMNL death could be related to the ability of M. fermentans to penetrate host cell membranes.
A randomized comparative open study of the effects of two oral contraceptives, Triphasil and Ortho 7/7/7, on lipid metabolism.
This study assessed serum lipid, lipoprotein and apolipoprotein changes during one year in 3 groups of nonsmoking women: 1) Triphasil(R); 2) Ortho(R) 7/7/7; 3) Controls. Both oral contraceptives contain the estrogen, ethinyl estradiol(EE), in combination with a progestin in three different ratios during each cycle. The progestin in Triphasil is d-norgestrel, as the dl-racemate norgestrel (NG), whereas that in Ortho 7/7/7 is norethindrone(NE). Total plasma triglycerides were elevated significantly from baseline (p < 0.001) with Ortho 7/7/7 at 3, 6 and 12 months, but only at 3 months with Triphasil, p = 0.047. Triglycerides were elevated in the LDL fraction with Ortho 7/7/7 at 3 months (p = 0.001), 6 months (p = 0.018) and 12 months (p = 0.010). In contrast, LDL triglycerides were not significantly elevated with Triphasil. Similarly, IDL triglycerides were elevated only in the Ortho 7/7/7 group at 6 months (p = 0.002) and 12 months (p = 0.001). Plasma cholesterol was elevated only in the Ortho 7/7/7 group at 3, 6 and 12 months with p values of 0.009, 0.005 and 0.010, respectively. Cholesterol in the LDL fraction was elevated with Ortho 7/7/7 at 12 months (p = 0.002). Plasma apolipoprotein B (apo B) increased at least 24% from baseline for both the Triphasil and Ortho 7/7/7 groups at 3 and 12 months (p < 0.001). However, at 6 months, apolipoprotein B increased only 17.7% (p = 0.008) with Triphasil compared to 29.7% (p < 0.001) with Ortho 7/7/7 at 6 months. Apo B was increased (p < 0.001) in LDL with Triphasil at 3 months only, whereas LDL apo B was increased at 3, 6 and 12 months with Ortho 7/7/7 (p < 0.001, p = 0.020 and p = 0.012, respectively). Apo B increased dramatically in the IDL fraction of both oral contraceptive user populations, with the range of increases being between 48% and 87% during the year (p < 0.001 at all times). Significant elevations in VLDL apo B ranged from 71% to 106% (p < 0.001) with Triphasil and from 42.4% (p < 0.005) to 72.6% (p < 0.001) with Ortho 7/7/7. In conclusion, norethindrone- and dl-norgestrel-formulations have divergent effects on several components of plasma lipoprotein and lipid metabolism, but both products increase plasma and IDL apo B.
Migraine madness: recurrent psychosis after migraine.
A 69 year old man with longstanding migraine with aura had four episodes of psychosis lasting 7-28 days during a 17 year period. During attacks he had formed visual hallucination and delusions, including reduplicative paramnesia. His mother was similarly affected. His EEG showed symmetrical frontal delta waves. The time course and EEG changes are similar to acute confusional migraine. The reduplicative paramnesia suggests a focal non-dominant hemisphere dysfunction.
Urinary clusterin in chronic nephrotoxicity in the rat.
The excretion of clusterin was compared with that of N-acetyl-beta-glucosaminidase (NAG) in rats given gentamicin daily for 2 months to determine whether clusterin excretion stays elevated after NAG excretion falls during chronic gentamicin administration. Clusterin was measured by radioimmunoassay and NAG by the hydrolysis of 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide. Gentamicin at 110 mg/kg was given daily for 44 days and thereafter, at 90 mg/kg daily. The excretion rate of both proteins rose rapidly, peaked, and then declined; however, the clusterin values stayed significantly above control values for the entire study, whereas NAG values were close to normal during the last 10 days, even though tubulointerstitial disease was active at that time. For this reason, the further evaluation of clusterin as a marker of renal tubular cell injury or death is warranted.
Transplantation--the issues: a cross curriculum programme for secondary schools.
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Fermi surface and band structure of ferromagnetic cobalt.
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Decision analysis in medicine.
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Antihypertensive and hemodynamic effects of calcium channel blockade with isradipine after acute exercise.
In a randomized, double-blind, placebo-controlled, crossover study with two 4-week treatment periods, we investigated the effects of calcium channel blockade with 5 mg slow release oral isradipine on postexercise blood pressure and systemic hemodynamics (echocardiography) in ten hypertensive patients. The results show that the combination of exercise and isradipine treatment exerts additive antihypertensive effects in hypertensive patients after exercise. The antihypertensive effect of prior exercise with placebo was related to a significant fall in total peripheral resistance. After exercise during isradipine treatment, total peripheral resistance was lower than with placebo. Thus, isradipine exerts an additional antihypertensive effect during the postexercise period, which appears to be mediated by a further reduction of total peripheral resistance.