Biomedical subjects

C Hunt

Publications and source records attributed to C Hunt.

At least 55 records · Page 3Linked to original sources

PubMed1994

Taxol causes rapid gross structural rearrangement of a native microtubule bundle.

Taxol is an anti-mitotic agent now being used in the treatment of some cancer, although the manner of its interaction with the microtubular components of the cytoskeleton is still not fully characterized. Here we report the effects of taxol upon a huge, naturally occurring and experimentally amenable aggregate of parallel microtubules from the ovaries of hemipteran insects. Within seconds of exposure to taxol, the microtubule aggregate began to twist upon itself. After a few minutes this movement was complete, the drug having brought about a gross rearrangement of the microtubules, involving coiling on a massive scale. The final form assumed by the microtubule array was influenced by pH and by the presence of microtubule-associated proteins, salt, cations, and both hydrolysable and non-hydrolysable nucleotides. The possible mechanisms leading to this rapid structural change are considered.

Animals↗

PubMed1994

Role of MAPs and motors in the bundling and shimmering of native microtubules from insect ovarioles.

Bundles of native microtubules isolated from the ovarioles of hemipteran insects are seen to shimmer when observed using dark-field microscopy. This novel form of microtubule motility becomes even more obvious when the isolated bundles are detergent-extracted and reactivated. We have studied the nucleotide-specificity and the drug-sensitivity of microtubule shimmering in order to obtain information regarding the nature of the motor protein responsible, and to compare its properties with those of previously characterised microtubule motors. The involvement of structural MAPs in the shimmering and in maintenance of microtubule bundles in this system has also been investigated.

Adenosine Triphosphate↗

PubMed1994

P1 and cosmid clones define the organization of 280 kb of the mouse H-2 complex containing the Cps-1 and Hsp70 loci.

A 280 kilobase (kb) contig was isolated from mouse genomic P1 and cosmid libraries, using as probes human cDNA and genomic DNA fragments that map in the interval between the second component of complement and tumor necrosis factor genes of the HLA complex. The clone contig demonstrates synteny of eleven mouse genes that are homologous to genes initially mapped within the human major histocompatibility complex. These include the mouse homologs of BAT2 (HLA-B-associated transcript 2) through BAT9 and also three HSP70-related genes. Five P1 clones form a contig of 240 kb that spans from BAT9 through BAT3. Twelve cosmid clones are arranged in three contigs that confirm most of the structure of the P1 contig and link the mouse BAT3 homolog to the BAT2 homolog approximately 15 kb farther telomeric. Polymorphic DNA markers within the cloned region were used to map the cleft palate susceptibility-1 (Cps-1) locus to the interval between Hsp70.1 and BAT6 (valyl-tRNA synthetase). This refines the location of the Cps-1 locus to a 45 kb region contained in the H2-124 P1 insert.

Adenosine Triphosphatases↗

PubMed1994

Lyme disease: a search for a causative agent in ticks in south-eastern Australia.

Attempts were made to identify the causative organism of Lyme disease in Australia from possible tick vectors. Ticks were collected in coastal areas of New South Wales, Australia, from localities associated with putative human infections. The ticks were dissected; a portion of the gut contents was examined for spirochaetes by microscopy, the remaining portion inoculated into culture media. The detection of spirochaetes in culture was performed using microscopy, and immunochemical and molecular (PCR) techniques. Additionally, whole ticks were tested with PCR for spirochaetes. From 1990 to 1992, approximately 12,000 ticks were processed for spirochaetes. No evidence of Borrelia burgdorferi or any other spirochaete was recovered from or detected in likely tick vectors. Some spirochaete-like objects detected in the cultures were shown to be artifacts, probably aggregates of bacterial flagellae. There is no definitive evidence for the existence in Australia of B. burgdorferi the causative agent of true Lyme disease, or for any other tick-borne spirochaete that may be responsible for a local syndrome being reported as Lyme disease.

Animals↗

PubMed1994

The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections.

A randomised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell vitamin C concentrations on admission. Various mechanisms by which vitamin C could assist this type of patient are discussed.

Acute Disease↗

PubMed1994

The limited value of cytoreductive surgery in elderly patients with malignant gliomas.

In this retrospective, consecutive series of 128 elderly patients (over 65 years of age) with histologically proven Grade 4 astrocytomas, 88 patients underwent stereotactic biopsy and 40 patients underwent stereotactic volumetric resection of the mass lesion defined by contrast enhancement on computed tomography. There were no significant differences in age (average age in the biopsy group, 71.6 yr; resection group, 70.15 yr) or Karnofsky Performance Scores (biopsy group, 84.33; resection group, 83.88) between the two groups. Four of the biopsy patients and one of the resection patients died within 30 days of surgery. The overall mean survival was 126 days; 108 days (15.4 wk) in the patients who had biopsies and 189 days (27 wk) in the patients who had resections. Radiation therapy was completed in 62 of the patients who had biopsies (mean survival, 118 d or 16.9 wk) and 34 of the patients undergoing resection (mean survival, 210 d or 30 wk) (log rank P = 0.0215; Smirnov P = 0.006). Although some prolongation of survival is noted after resection (more than after a biopsy) in selected patients over 65 years of age, that benefit is modest.

Aged↗

PubMed1993

Inclusion body myositis: an underdiagnosed condition?

Inclusion body myositis is an increasingly recognised form of inflammatory myopathy with characteristic clinical and histopathological features which has seldom been reported in the United Kingdom. This paper presents the clinicopathological features of a series of patients diagnosed in Nottingham from 1986 to 1990. During this period, 1319 muscle biopsy samples were processed by this laboratory and rimmed vacuoles were seen in 17 patients. Eleven patients had definite or probable inclusion body myositis according to published criteria. The mean age of the group was 69.4 years with a male to female ratio of 8:3. Typical clinical features were a slowly progressive painless, proximal lower limb weakness, with muscle wasting and early loss of reflexes. The median duration of illness from first symptom to presentation was five years (range 2-18 years). Falls were a prominent symptom in six patients and distal weakness occurred in nine patients. Creatine kinase was increased in 10 patients but only one had a level > 1000 IU/l; the erythrocyte sedimentation rate was normal in five patients. Treatment with steroids or cytotoxic drugs, or both, did not prevent disease progression. It is confirmed that inclusion body myositis is a distinct cause of inflammatory myopathy which is probably underdiagnosed in the United Kingdom. Clinically, it should be suspected in older patients presenting with muscle weakness of insidious onset. Pathologically, a careful search should be made for rimmed vacuoles and inflammation; ultrastructurally, the presence of inclusions will confirm the diagnosis.

Aged↗

PubMed1993

A novel morphine sulphate preparation: clinical trial of a controlled-release morphine suspension in cancer pain.

In order to determine the efficacy of a novel controlled-release morphine suspension, we performed two prospective sequential open-label studies in patients with pain due to cancer. The studies were identical except for the duration of treatment (three days and 30 days respectively). Sixty-nine patients with a variety of advanced cancers and associated pain participated. Fifty-three patients completed the trials, 38 on the three-day trial and 15 on the 30-day trial. In both groups the amount of morphine required to obtain pain relief was initially established using controlled-release morphine tablets and immediate-release morphine for 'rescue' dosing. Patients were begun on equivalent doses of the study drug in place of the controlled-release tablets. No differences in pain score or the amount of 'rescue' morphine were noted following the switch to the controlled-release morphine suspension. Toxicity was as anticipated for the use of morphine in this situation and no adverse effects were observed during administration of the suspension. These data suggest that this new formulation of morphine is equipotent to conventional controlled-release morphine tablets and provides pain relief for a 12-hour dosing interval. This novel morphine formulation could be especially useful for paediatric patients and for those who have difficulty in swallowing.

Adult↗

PubMed1992

High molecular weight microtubule-associated proteins within testes of hemipteran insects.

Results presented here indicate that the high molecular weight microtubule-associated proteins isolated from the ovaries of the hemipterans, Oncopeltus fasciatus and Notonecta glauca, while absent from nervous tissue, are present in the testes of the respective species. Here they are seen to be located to extensive microtubule aggregates within the cells surrounding the sperm, but not obviously to the sperm themselves.

Animals↗

PubMed1992

Drop-out rate as a performance indicator in psychotherapy.

Many large studies of psychotherapy show that the median patient drops out by the 5th session and most before the 10th session. Data from an effective behavior therapy clinic for the anxiety disorders showed that only 17% of patients failed to complete a median of 60 h of therapy. Patient characteristics were not associated with attrition. We examined 5 meta-analytic treatment reviews and found the median drop-out rate was 8% after 20 h of therapy. We suggest that low attrition is associated with effective, standardized treatment and as such, drop-out rate may be a proxy variable that can indicate effective service delivery.

Adult↗

PubMed1991

Butorphanol compared with fentanyl in general anaesthesia for ambulatory laparoscopy.

Butorphanol was compared with fentanyl as the narcotic component of general anaesthesia for ambulatory laparoscopic surgery. This double-blind, randomized study enrolled 60 healthy women who received equianalgesic doses of fentanyl 1 microgram.kg-1 (F, n = 30) or butorphanol 20 micrograms.kg-1 (B, n = 30) prior to induction of anaesthesia. Tracheal anaesthesia was maintained with nitrous oxide/oxygen, isoflurane, and succinylcholine by infusion. Intraoperatively, patients who received B demonstrated lower pulse rate before and after intubation (P less than 0.05, P less than 0.01) and lower diastolic blood pressure after intubation (P less than 0.01). Anesthesiologists judged the maintenance phase as satisfactory more often with B (P less than 0.05). Postoperatively, there were no differences in analgesic need. No major side-effects occurred in either group. Among minor side-effects, patients who received B reported postoperative sedation more often, 77% vs 37% (P less than 0.01), which occurred during the first 45 min of recovery (P less than 0.05). Discharge times were not different. On the first postoperative day, more subjects who received B were satisfied with their anaesthesia experience (P less than 0.05). Butorphanol 20 micrograms.kg-1 is an acceptable alternative analgesic in general anaesthesia for ambulatory laparoscopy.

Adult↗

PubMed1991

MAPs and motors in insect ovaries.

MAPs and microtubule motor proteins from the massive microtubule translocation complexes within the ovaries of hemipteran insects have been identified and characterized. Both classes of proteins have been compared with those of other systems, and the function of both in the insect ovaries is speculated upon.

Animals↗

PubMed1990

Characterization and sequence of a mouse hsp70 gene and its expression in mouse cell lines.

A heat-inducible member of the mouse hsp70 gene family has been isolated and characterized. The gene, hsp70.1, has a primary transcript of 2.8 kb before and 3.1-3.5 kb after polyadenylation. It includes a 645-nucleotide (nt) 3'-nontranslated terminus and a 225-nt 5' leader. The leader sequence is unusual in that it contains a 33-nt triple tandem repeat element proximal to the ATG codon. As expected, a single open reading frame encodes a 642-amino acid (aa) 70-kDa protein with 95% aa homology and 91% nt homology to a human hsp70 gene. While there is no homology through the 5'- and 3'-nontranslated regions, the human and mouse hsp70 gene promoters can be aligned to give 65% homology. Of three mouse cell lines studied, two expressed the 3.1- to 3.5-kb mRNA during heat shock. One line also expressed an additional, smaller, 2.6-kb hsp70 mRNA transcribed from a separate gene(s). Mouse erythroleukemia cells were unresponsive to heat shock, with neither hsp70 RNA being induced by heat shock. These results suggest that cell lineage has a major influence on the cellular response to heat shock and that the response is not universal in all cell types.

Amino Acid Sequence↗

PubMed1990

In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes.

Some quinolone antibiotics cause increases in levels of theophylline in plasma that lead to serious adverse effects. We investigated the mechanism of this interaction by developing an in vitro system of human liver microsomes. Theophylline (1,3-dimethylxanthine) was incubated with human liver microsomes in the presence of enoxacin, ciprofloxacin, norfloxacin, or ofloxacin. Theophylline, its demethylated metabolites (3-methylxanthine and 1-methylxanthine), and its hydroxylated metabolite (1,3-dimethyluric acid) were measured by high-pressure liquid chromatography, and Km and Vmax values were estimated. Enoxacin and ciprofloxacin selectively blocked the two N demethylations; they significantly inhibited the hydroxylation only at high concentrations. Norfloxacin and ofloxacin caused little or no inhibition of the three metabolites at comparable concentrations. The extent of inhibition was reproducible in five different human livers. Inhibition enzyme kinetics revealed that enoxacin caused competitive and mixed competitive types of inhibition. The oxo metabolite of enoxacin caused little inhibition of theophylline metabolism and was much less potent than the parent compound. Nonspecific inhibition of cytochrome P-450 was ruled out since erythromycin N demethylation (cytochrome P-450 mediated) was unaffected in the presence of enoxacin. These in vitro data correlate with the clinical interaction described for these quinolones and theophylline. We conclude that some quinolones are potent and selective inhibitors of specific isozymes of human cytochrome P-450 that are responsible for theophylline metabolism. This in vitro system may be useful as a model to screen similar compounds for early identification of potential drug interactions.

Biotransformation↗

PubMed1990

Diagnosis, personality and the long-term outcome of depression.

Patients diagnosed in the late 1960s as suffering from either endogenous or neurotic depression, or as presenting with depression but discharged with another neurotic diagnosis, were followed for 15 years. Diagnosis at index admission did not predict overall outcome, but patients with endogenous depression, an apparently stable diagnosis, had longer index admissions, were readmitted sooner, but spent less time ill than patients in either of the neurosis groups. Personality abnormality accounted for 20% of the variance in outcome in the neurotic groups and only 2% of the variance in the endogenous group. Thus there is evidence that endogenous and neurotic depression are two illnesses and that, in the neuroses particularly, prognosis will depend on the extent to which these personality abnormalities are modified by treatment.

Depressive Disorder↗

PubMed1989

Giemsa staining for cysts and trophozoites of Pneumocystis carinii.

Although Giemsa staining has been routinely used for the detection of trophozoites and intracystic bodies in smears of bronchoalveolar lavage fluid (BAL) from patients with Pneumocystis carinii pneumonia, it does not normally stain the cyst wall. For detection of the cysts other stains such as toluidine Blue 'O' and methenamine silver must be used as well. Sulphation of smears before staining with Giemsa allows cysts to be visualised, thus enabling a single stain to be used to show all the stages of BAL or sputum, which is particularly useful, considering the increase in the prevalence of P carinii pneumonia in conjunction with the spread of AIDS.

Animals↗

PubMed1989

Prophylactic antibiotics in trauma: the hazards of underdosing.

Prophylactic antibiotic regimens in trauma patients may be significantly altered by large fluid shifts and hyperdynamic physiologic responses. We prospectively studied prophylactic amikacin and clindamycin in 150 abdominal trauma patients requiring laparotomy, analyzing the effects of duration of coverage, dosing interval, and dose. No difference in infection rates was noted when 72-hour coverage was compared with 24-hour coverage (19% vs. 21%). Clindamycin dosed at 1,200 mg every 12 hours achieved acceptable serum concentrations; infection rates were not significantly higher than seen with 600 mg every 6 hours (21% vs. 12%, p greater than 0.05). High-dose (11 mg/kg) amikacin reduced infection rates in patients with high blood loss (p less than 0.025), high Injury Severity Scores (p less than 0.025), and no colon penetration (p less than 0.005). These data suggest that high doses are more effective than long courses of antibiotics in reducing infections in trauma patients undergoing laparotomy.

Abdominal Injuries↗

PubMed1987

Binding of mammalian brain microtubule-associated proteins (MAPs) to insect ovarian microtubules.

In this study we have applied microtubule-associated proteins (MAPs) from mammalian brain to both native and reassembled insect ovarian microtubules. Such microtubules, which are normally smooth walled, become decorated with projections similar to those observed when mammalian brain MAPs are added back to assembling or assembled mammalian brain microtubules. The mammalian MAPs were also detected as components of insect microtubules when analyzed by polyacrylamide gel electrophoresis. Our observations suggest that mammalian brain MAPs have common binding sites on microtubules from two widely different sources and indicate the degree of evolutionary conservation of such sites.

Animals↗