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Biomedical subjects

M Harper

Publications and source records attributed to M Harper.

At least 73 records · Page 4Linked to original sources

HTLV-I infection of cerebrospinal fluid T cells from patients with chronic neurologic disease.

Antibodies reacting with HTLV-I, the etiologic agent of acute T cell leukemia/lymphoma and a transforming agent for T4-positive lymphocytes in vitro, have recently been described in sera of patients with chronic neurologic disease in the absence of lymphoproliferative disorders. The largest number of such cases was described in Japan and in the Caribbean and parts of South America. We report here two cases of patients with chronic neurologic disease whose cerebrospinal fluid (CSF)-derived T cells contain HTLV-I specific RNA sequences and antigens and are expressing retroviral particles. Only one of these patients has demonstrable antibody to HTLV-I in serum or CSF.

Adult↗

Possible toxic metal exposure of prehistoric bronze workers.

An attempt has been made to assess the possible occupational exposure to arsenic, lead, and mercury during the Bronze Age. Archaeological, metallurgical, and historical evidence is combined to form a picture of the potential toxic hazards. In the case of arsenic a definite picture emerges of the effect of toxicity as a useful material is abandoned for health reasons on discovery of an acceptable alternative.

Alloys↗

Vasopressin-resistant diabetes insipidus, liver dysfunction, hyperuricemia and decreased renal function. A case report.

A case of transient nephrogenic diabetes insipidus occurred in late pregnancy, the first associated with biopsy-proven hepatitis. Five previously reported cases occurred in pregnancy. All six patients demonstrated similar but transient signs, symptoms and laboratory abnormalities suggesting a syndrome peculiar to pregnancy. The characteristics of this syndrome are elevated liver function studies, decreased renal function, hyperuricemia and transient vasopressin-resistant diabetes insipidus.

Adult↗

Immediate and short-term benefit of multilesion coronary angioplasty: influence of degree of revascularization.

The safety and short-term therapeutic benefit of multilesion percutaneous transluminal coronary angioplasty was assessed in 135 patients, 66 of whom had a minimum of 6 months of follow-up study. Primary success, defined as successful dilation of the most critical lesion or all lesions attempted without major in-hospital complications was obtained in 117 (87%) of the 135 patients. Cardiac complications associated with the procedure were uncommon; prolonged angina occurred in 5% and myocardial infarction in 3%; emergency coronary bypass surgery was performed in 4% of the patients. There were no deaths. Complete revascularization was achieved in 46% of the 117 patients with a primary success. Of the 66 patients eligible for 6 month follow-up, 80% had an uncomplicated course and required no further procedures. Clinical improvement by at least one angina functional class was observed in 90% of the patients. Cardiac events such as the need for a second revascularization procedure were significantly more common in patients who had incomplete versus complete revascularization (35 versus 9%; p = 0.018). Repeat coronary angiography performed an average of 5 months after angioplasty revealed restenosis in 18 of 22 symptomatic patients and 3 of 9 asymptomatic patients. Restenosis occurred at the site of a single dilation in 12 patients, at two sites in 8 patients and at three sites in 1 patient. Thus, multilesion coronary angioplasty is an important therapeutic option for selected patients with multivessel disease and can be performed with relatively low risk. Improvement in angina status can be expected even in patients who have incomplete revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular biology of human T-lymphotropic retroviruses.

The generic name for a family of human T-lymphotropic retroviruses is HTLV. Two of the three members in this family have been linked etiologically to human diseases: HTLV-I with adult T-cell leukemia and HTLV-III with the acquired immunodeficiency syndrome. In addition to their T-cell tropism and a number of other common biological and biochemical properties, the most unique common features of these viruses from a molecular biological point of view are the presence of the x-lor gene towards the 3' end of the genome and the phenomenon of a virus-induced trans-acting factor in activation of transcription initiated in the viral long terminal repeat. These features may not only be key in understanding the mechanism of transformation or cell killing by these viruses, but they also provide a basis for new classification of retroviruses. In spite of these similarities among HTLV-I, -II, -III, and bovine leukemia virus, the genome of HTLV-III is only distantly related to these other viruses. Instead, it shows greater homology to members of the Lentivirus family. Therefore, all these viruses may have a common progenitor. Two other salient features arose from the analyses of HTLV-III and acquired immunodeficiency syndrome. (a) HTLV-III frequently infects the brain of acquired immunodeficiency syndrome patients who suffer from central nervous system disorders. This not only identifies HTLV-III as the direct candidate in these central nervous system disorders but also poses the problem of crossing the blood-brain barrier in therapy strategies to eradicate the virus. (b) Different HTLV-III isolates comprise a spectrum of related viruses, with the degree of divergence varying from virtual identity to 10-15% difference. The most divergent region resides in the envelope gene. Whether this finding has implications in the development of an effective vaccine for acquired immunodeficiency syndrome remains to be determined.

Acquired Immunodeficiency Syndrome↗

Molecular characterization of human T-lymphotropic leukemia virus type III associated with the acquired immunodeficiency syndrome.

A T-lymphotropic retrovirus with cytopathic but not immortalizing activity has been isolated repeatedly from patients with acquired immune deficiency (AIDS) or lymphadenopathy syndrome (LAS) and successfully transmitted to a T-cell line (HT) for continuous production. Seroepidemiology data and the OKT4 tropism and cytopathogenicity of this virus indicate it is the etiological agent of AIDS. We have cloned HTLV-III genomes using three approaches: (1) cDNA clones were obtained from a cDNA plasmid library constructed from RNA of purified virions using oligo (dT) primers; (2) unintegrated provirus clones were obtained from Hirt supernatants of acutely infected H9 cells using virus from H9/HTLV-III; (3) clones of integrated provirus with flanking cellular sequences were obtained from a genomic DNA library of H9/HTLV-III. Analyses of these clones show that the HTLV-III genome is similar in size to those of HTLV-I and HTLV-II and contains a gene that functions as a transcriptional activator. Different isolates of HTLV-III display greater polymorphism than different isolates of HTLV-I among each other, possibly due to the highly replicative nature of HTLV-III. Viral sequences could be detected in fresh lymph node tissues of some AIDS patients, but even in the positive samples the number of infected cells is small (less than 1%). In both fresh tissues that are positive for viral sequences and HTLV-III infected cell lines, a substantial amount of unintegrated viral DNA is present in addition to integrated provirus. This is an unusual finding for retroviruses but may be significant in the cytopathicity of HTLV-III as has been proposed for some avain retroviruses.

Acquired Immunodeficiency Syndrome↗

Near-total pancreatectomy for chronic pancreatitis.

Eighty-seven patients underwent distal subtotal or near-total (80% to 95%) pancreatectomy (NTP) during a 25-year period for management of intractable pain resulting from chronic pancreatitis. Alcoholism affected the majority of patients and 20% of cases were idiopathic in origin. Ten patients (12%) exhibited insulin-requiring diabetes before operation. The perioperative mortality rate was 3.4%. Significant improvement or complete pain relief was achieved in 75% of patients while 14% remained narcotic dependent. Forty-four patients (51%) required insulin postoperatively, with an average insulin requirement of 35 U per day. Thirty late deaths occurred 2 to 15 years after operation, 12 (40%) of which were related to complications of pancreatic insufficiency or persistent alcoholism. Five patients (8.5%) required completion pancreatectomy 6 months to 4 years after NTP for complications relating to persistent pancreatitis. NTP provides effective pain relief in the majority of patients with chronic pancreatitis. While this procedure can be performed with a low operative mortality rate, the high incidence of endocrine and exocrine insufficiency after operation may contribute to late deaths. Consequently, this procedure should be performed only when the underlying disease has functionally destroyed the pancreas or when lesser procedures have failed to provide adequate pain relief.

Adolescent↗

Adhesion of fimbriate Escherichia coli to bovine mammary-gland epithelial cells in vitro.

The adhesion of bovine and a human isolate of Escherichia coli to epithelial cells from the teat and lactiferous sinuses of the udder was examined. Adhesion was detected with bacterial suspensions that produced mannose-sensitive agglutination of guinea-pig red cells. Adhesion to epithelial cells could be inhibited by mannose and the degree of adhesion occurring with a suspension correlated with its haemagglutinating activity. This demonstrated that fimbriae were responsible for the adhesion. The observation that whole milk inhibited attachment of E. coli to cells in vitro indicates that such attachment may not occur in vivo in the lactating cow.

Animals↗

X-chromosome activity in preimplantation mouse embryos from XX and XO mothers.

Embryos from XO female mice begin development with half the activity levels of an enzyme (HPRT) coded for by a gene on the X chromosome, compared with embryos from XX females. Groups of unfertilized eggs and individual embryos at the 8-cell, morula and blastocyst stages were assayed for HPRT activity. An autosomally coded enzyme (APRT) was assayed simultaneously in the same reaction mix as a control. There is a substantial increase in HPRT activity by the 8-cell stage. However, the mean activity of HPRT in embryos of XO mothers remains half that in embryos of XX mothers. This suggests a significant maternally inherited component of HPRT activity in 8-cell embryos. By the 9- to 16-cell morula stage the HPRT activities in the two groups of embryos become similar due, presumably, to a transition to embryo-coded activity; HPRT activities in individual morulae from XX mothers show a bimodal distribution consistent with the hypothesis that both X-chromosomes are active in XX embryos at this stage.

Adenine Phosphoribosyltransferase↗

Immediate post-placental insertion of intrauterine contraceptive devices.

Insertion of one of three types of intrauterine contraceptive device--the Lem, copper 7, and 'Progestasert' system--was carried out in 274 obstetric patients. These devices were all inserted within 20 min of delivery of the placenta and membranes, with a special 25 cm inserter. The expulsion-rate was low (less than 7%), and there were no uterine perforations. There was no difference in puerperal morbidity between these patients and a matched control group, and no cases of pelvic sepsis developed.

Contraception↗

Effect of carotid ligation on cerebral blood flow in baboons. 2. Response to hypoxia and haemorrhagic hypertension.

Cerebral blood flow (CBF) measurements were carried out in two groups of anaesthetized normocapnic baboons. In the first group of five animals the effect of hypoxia on the CBF before and after ipsilateral carotid artery ligation was studied. The results showed that, although after ipsilateral carotid ligation there was little change in the CBF at normal PaO(2), at hypoxia there was only 20% rise in the CBF as compared with an 80% rise before the carotid ligation. In the second group of 10 animals, effects of haemorrhagic hypotension on the CBF after ipsilateral carotid artery ligation were estimated. The results indicated impairment of autoregulatory response of the cerebral circulation.

Animals↗

Independent antibiotic actions of hetacillin and ampicillin revealed by fast methods.

Fast methods for measuring inhibition of growth of Escherichia coli or Staphylococcus aureus by hetacillin or ampicillin showed that the rate of inhibition was a function of the antibiotic concentration. When ampicillin concentrations were measured rapidly, hetacillin was shown to have a half-life of 20 min at 37 C and pH 6.7. Hetacillin was much less susceptible to penicillinase (beta-lactamase) than was ampicillin. An inhibitory effect of hetacillin was shown in the presence of beta-lactamase, which destroyed ampicillin activity very rapidly.

Ampicillin↗

Effect of carotid ligation on cerebral blood flow in baboons. I. Response to altered arterial PCO2.

Measurements of cerebral blood flow (CBF) were made in anaesthetized baboons before and after ipsilateral carotid artery ligation and also after bilateral carotid ligation. Results showed that at normocapnia (PaCO(2) 38-39 mmHg) there was little change in cerebral blood flow on ipsilateral carotid ligation, but when both carotid arteries were tied the blood flow to the brain fell significantly. At hypercapnia (PaCO(2) 58-60 mmHg) the CBF/CO(2) gradient fell significantly on ipsilateral carotid ligation; on bilateral carotid ligation there was only minimal rise in cerebral blood flow in response to the rise in PaCO(2). At hypocapnia (PaCO(2) 20-21 mmHg) the gradients of fall in the CBF were similar before and after ipsilateral carotid ligation; after bilateral carotid ligation there was minimal change in the CBF in response to the fall in the PaCO(2). It is suggested that, although cerebral blood flow may be normal after ipsilateral carotid ligation, the circulatory reserve of the brain is not sufficient to meet physiological challenges. This may be the reason for the development of delayed neurological complications after carotid artery ligation.

Animals↗