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Biomedical subjects

A MacLean

Publications and source records attributed to A MacLean.

27 records · Page 2Linked to original sources
PubMed1991

The HSV-1 latency associated transcript (LAT) variants 1704 and 1705 are glycoprotein C negative.

The latency associated transcripts (LAT) of herpes simplex virus type 1 (HSV-1) are encoded by diploid genes that are expressed during latent infections. Two LAT variant viruses, 1704 and 1705, were compared with the parental strain 17+. Variant 1705 has a deletion affecting one copy of the LAT genes, expresses LATs during latent infection and reactivates normally. Variant 1704 has deletions affecting both LAT gene copies, does not express LATs during latent infection, and its reactivation is impaired (Steiner et al., 1989). Comparison of infected cell proteins by immunoprecipitation and Western blot analysis revealed one significant difference between HSV-1 strain 17+, 1704 and 1705; glycoprotein C (gC) was not synthesized by 1704 or 1705. Since both 1704 and 1705 are gC minus, the reactivation defect of 1704 is most likely related to the absence of the LATs, and not to the absence of gC.

Animals↗
PubMed1991

The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency.

We have demonstrated that the variant JH2604 of the herpes simplex virus type 2 (HSV-2) strain HG52 is completely avirulent in BALB/c mice following intracranial inoculation, with an LD50 of greater than 10(7) p.f.u./mouse compared to the wild-type LD50 of less than 10(2) p.f.u./mouse. In JH2604, a 1.5 kbp deletion extends from the DR1/Ub junction of the 'a' sequence to 511 bp upstream of the 5' end of IE1 in both long repeats. We have since constructed a second variant (2701) in which only 850 bp are removed from the RL. This deletion lies entirely within the sequences deleted in JH2604 and leaves intact most of a short 189 bp open reading frame (ORF) highly conserved between HSV-1 and HSV-2. Like JH2604, 2701 shows wild-type growth characteristics and is neither host range- nor temperature-restricted. This was most noteworthy in the case of mouse 3T6 cells. 2701 has an LD50 of 5 x 10(5) p.f.u./mouse on intracranial inoculation, a value intermediate between those of HG52 and JH2604. In assays for intracranial replication, JH2604 exhibits no detectable growth with a rapid decline in virus titre, 2701 shows limited growth over the first 24 to 36 h post-inoculation before the titre again declines and HG52 grows rapidly, reaching a high titre until the mice die. Taken together these results suggest that a region of the genome upstream of IE1 encodes a gene product essential for HSV replication in neurons of the central nervous system. It is highly likely that the conserved ORF is in an important region of a polypeptide essential for neurovirulence, although the upstream sequences present in 2701 but absent from JH2604 must also play a role. Although JH2604 and 2701 are avirulent, they both establish latent infection in the dorsal root ganglia of BALB/c mice and reactivate in vitro in a manner indistinguishable from HG52. This suggests a distinct separation of the factors involved in neurovirulence and the establishment of/reactivation from latency.

Animals↗
PubMed1988

A pilot study of carboplatin (JM8, CBDCA) and chlorambucil in combination for advanced ovarian cancer.

Forty-six patients with previously untreated, advanced ovarian cancer received carboplatin (JM8, CBDCA) and chlorambucil (CLB) to assess the efficacy and toxicity of this combination. Carboplatin 300 mg m-2 was given on day 1 with CLB 10 mg daily for 7, 10 or 14 days; 6 treatment courses were given at 4-6 weekly intervals in the absence of disease progression. Tumour response was assessed, where possible, by restaging laparotomy after 6 treatment cycles. Five complete and 16 partial remission were seen in 37 evaluable patients giving an overall response rate of 57%. The median survival of all patients was 15 months. The major toxicity was myelosuppression. Nausea and vomiting were generally minor (WHO, grades I or II) and most courses were given on an outpatient basis. Leucopenia was the major factor causing treatment delays, particularly with the 10 and 14 day CLB regimens. Thrombocytopenia was minimal in the early chemotherapy cycles but the data suggest that cumulative toxicity may occur. This combination may provide a satisfactory degree of efficacy with less toxicity than cisplatin-based regimens.

Adult↗
PubMed1987

Mood change following an acute delay of sleep.

A phase advance of some circadian rhythms (e.g., body temperature and rapid eye movement [REM] sleep propensity) relative to the sleep-wake cycle is thought to be implicated in the pathophysiology and pathogenesis of some affective disorders. Since this phase disturbance can be induced in normal subjects by acutely delaying their sleep onset, it follows that the outcome of this experimental procedure should resemble the symptoms of depressive illness. This hypothesis was tested by imposing a 6-hour phase delay of sleep in 10 young male subjects. There were reliable changes in observers' ratings of mood and in some self-report measures. For the most part, the effect was modest, being largely confined to variations within normal limits. Two of the subjects, however, were noticeably depressed when interviewed after either the first or the second night of phase shift.

Adult↗
PubMed1978

Bone response to termination of oestrogen treatment.

Forty-three oophorectomised patients were reviewed 8 years after their initial attendance at a research clinic investigating the aetiology and prevention of postmenopausal osteoporosis. Fifteen patients who had been treated with an oestrogen did not lose a significant amount of bone during the 8 years of therapy. Patients in the placebo-treated control group initially had bone loss of 2.6% per annum, which later fell to an average of 0.75% per annum. Fourteen patients who had been treated with oestrogen for the first 4 years lost no bone, but on withdrawal of oestrogen their bone mineral content fell over the next 4 years at an average rate of 2.5% per annum. 8 years after their initial attendance there was no significant difference between this group and patients who had received placebo for the full 8 years. The result of this study indicates that long-term prevention of bone loss by oestrogens has important medical, social, economic implications.

Bone and Bones↗