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Biomedical subjects

J Morris

Publications and source records attributed to J Morris.

At least 361 records · Page 20Linked to original sources

The ageing hypothalamo-neurohypophysial system. An analysis of the neurohypophysis in normal hydration, osmotic loading and rehydration.

Age-associated changes in the structure and function of the neurohypophysis may contribute to the decreased ability to conserve water in older animals. We investigated the neurohypophyses of 6 and 28-month-old male mice using radioimmunoassay and quantitative morphological techniques. The dry-weight and volume of the neurohypophysis increased significantly with age but the quantity of vasopressin in the gland remained constant. Oxytocin levels decreased with age. A quantitative morphological analysis was performed on the compartments of the neurohypophysis from male mice of 6 and 28 months of age which were either normally hydrated, osmotically loaded, or osmotically loaded and rehydrated. The absolute volumes of the axon endings, swellings, their constituent organelles and the axon terminals containing degenerating subcellular components were determined. The design of the analysis allowed us to examine both age-related changes and statistical interactions between the age of the animal and the behaviour of a variable during the osmotic loading/rehydration phase of the experiment. There was a significant age-related reduction in the volume of the neurohypophysis occupied by the endings and swellings. The diameters of the neurosecretory granules found in the endings were significantly smaller than those in the swellings in both age groups but the size difference was greater in the young animals. Dehydration and subsequent rehydration of old male mice leads to extensive re-modelling of the neurohypophysial compartments and subcellular organelles to the configuration found in the adult animal.

Aging↗

Extending the duration of the pill-free interval during combined oral contraception.

The effect of increasing the duration of the pill-free interval from 7 to 9 and 11 days during the first 4 months of combined oral contraceptive therapy was studied by hormonal, ovarian follicle and mucus changes. Increasing the pill-free interval allowed more follicular development and more estradiol production. In some cases, pre-ovulatory values were achieved although ovulation did not occur. No differences could be detected between different types of combined oral contraceptive, including monophasic, triphasic, levonorgestrel-containing and gestodene-containing. The variation between individuals in the group of 28 was far greater than any variation in dose.

Adult↗

Cryopreservation and the maintenance of cell lines.

Techniques for cell-line preservation which enable reliable and reproducible recovery of material with unchanged, defined characteristics are essential in many biotechnology industries. Cryopreservation is one such technique, and in this review we explore some of its problems, successes and potential future applications.

Animals↗

Effect of autologous serum on human leucocyte Na+/H+ exchange and intracellular pH.

1. Leucocyte Na+/H+ exchange and intracellular pH were investigated in physiological buffer containing bicarbonate. 2. The amiloride analogue 5-(N,N-hexamethylene) amiloride (1 x 10(-5) mol/l), an inhibitor of Na+/H+ exchange, had no significant effect on resting leucocyte pH, Na+ influx or Na+ content. 3. Ammonium chloride washout induced a profound intracellular acidosis, stimulating Na+/H+ exchange. This led to a 236% increase in Na+ influx. Eighty-eight per cent of this increase was inhibited by 5-(N,N-hexamethylene) amiloride. This demonstrates that 5-(N,N-hexamethylene) amiloride is an effective inhibitor of Na+/H+ exchange in human leucocytes. 4. The recovery from intracellular acidosis was shown to be dependent entirely on the presence of extracellular Na+. The Ki for inhibition by 5-(N,N-hexamethylene) amiloride of the recovery was 0.5 mumol/l. 5. Incubation with serum increased Na+ influx and Na+ content: the maximal effect was reached at 20% dilution. Serum (10%, v/v) increased influx by 40%, and 20% (v/v) serum by 102%, over resting levels. Only 43% of the serum-induced increase in Na+ influx was inhibited by 5-(N,N-hexamethylene) amiloride. This represented one-fifth of total Na+ influx. 6. Leucocyte intracellular pH increased on incubation with serum. This alkalinization was inhibited using 5-(N,N-hexamethylene) amiloride. 7. Studies of Na+/H+ exchange in leucocytes in physiological and pathological states are more likely to reflect the state in vivo if carried out in the presence of autologous serum.

Amiloride↗

Identification of three related human GRO genes encoding cytokine functions.

The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate. One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide.

Amino Acid Sequence↗

Factors associated with risk behaviour among injecting drug users.

A project which investigated the injecting and sexual behaviour of drug users in the North West of England revealed several social and behavioural factors strongly associated with HIV-related risk behaviour. For example, homelessness, crime, ignorance of drug-related health problems and drug use by a regular partner were associated with the sharing of injecting equipment. Other variables predicted casual sexual intercourse and intercourse without condoms. Some factors were identified that were common to both injecting and sexual risk behaviour.

Adolescent↗

Sexual partners of injecting drug users: the risk of HIV infection.

The sexual mediation of HIV infection by injecting drug users to the heterosexual population has become a major issue in AIDS prevention. Infection that is acquired through sharing contaminated injecting equipment can be passed on to non-injecting drug using partners and to non-drug using partners through sexual intercourse. A study of risk behaviour among injecting drug users in the North West of England focused, inter alia, upon aspects of their sexual activity and attitudes that have relevance for HIV transmission. It was found that in those respondents with regular partners, the level of sexual activity was related to the partner's use of drugs. The use of condoms was low in the sample as a whole, including those who reported having casual sexual contacts and sharing others' injecting equipment. These data confirm the need for concern and the advisability of targetting safer-sex education on drug users.

Adult↗

AIDS-related risk behaviour, polydrug use and temazepam.

In a study of AIDS-related risk behaviour among injecting drug users in the north west of England it was found that 90% were polydrug users, and 28% were using temazepam. A third of all polydrug users had regularly used more than three drugs in addition to their preferred drug in the previous year. Statistical analysis revealed that the use of temazepam and extensive polydrug use were associated with sharing injecting equipment. Significant associations were also found with indices of sexual risk behaviour. It was concluded that multiple drug use and the use of temazepam were associated with behaviour that could increase exposure to HIV infection.

Acquired Immunodeficiency Syndrome↗

Identification of an additional ferric-siderophore uptake gene clustered with receptor, biosynthesis, and fur-like regulatory genes in fluorescent Pseudomonas sp. strain M114.

Five cosmid clones with insert sizes averaging 22.6 kilobases (kb) were isolated after complementation of 22 Tn5-induced Sid- mutants of Pseudomonas sp. strain M114. One of these plasmids (pMS639) was also shown to encode ferric-siderophore receptor and dissociation functions. The receptor gene was located on this plasmid since introduction of the plasmid into three wild-type fluorescent pseudomonads enabled them to utilize the ferric-siderophore from strain M114. The presence of an extra iron-regulated protein in the outer membrane profile of one of these strains was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A ferric-siderophore dissociation gene was attributed to pMS639 since it complemented the ferric-siderophore uptake mutation in strain M114FR2. This mutant was not defective in the outer membrane receptor for ferric-siderophore but apparently accumulated ferric-siderophore internally. Since ferric-citrate alleviated the iron stress of the mutant, there was no defect in iron metabolism subsequent to release of iron from the ferric-siderophore complex. Consequently, this mutant was defective in ferric-siderophore dissociation. A fur-like regulatory gene also present on pMS639 was subcloned to a 7.0-kb BglII insert of pCUP5 and was located approximately 7.3 kb from the receptor region. These results established that the 27.2-kb insert of pMS639 encoded at least two siderophore biosynthesis genes, ferric-siderophore receptor and dissociation genes, and a fur-like regulatory gene from the biocontrol fluorescent Pseudomonas sp. strain M114.

Bacterial Outer Membrane Proteins↗

Determinants of nocturnal enuresis in homozygous sickle cell disease.

The determinants of nocturnal enuresis in homozygous sickle cell (SS) disease have been investigated in 16 enuretic and 16 age and sex matched non-enuretic children. Overnight fluid deprivation tests (8pm-8am) demonstrated no significant difference in maximum urine osmolality or urine volumes, although the latter tended to be higher in the enuretic children. Maximum functional bladder capacity, estimated by maximum voided volume during oral fluid loading, was lower and the ratio of overnight urine volume to maximum functional bladder capacity higher in the enuretic than the non-enuretic group. Enuretic children were more likely than non-enuretics to be considered deep sleepers by their family. High urine volumes may contribute to nocturnal enuresis in SS disease, although the similar values in enuretic and non-enuretic children implies that additional factors determine the presence of enuresis. Low maximum functional bladder capacity, and a high ratio of overnight urine volume to maximum functional bladder capacity, appear to be important determinants.

Adolescent↗

Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. I. Abducens palsy.

Fifty one patients with abnormalities of horizontal gaze were studied with magnetic imaging of the brain (MRI) and eye movement recordings to identify the loci of lesions responsible for isolated abducens palsy, conjugate gaze palsy and different types of internuclear ophthalmoplegias. The lesions responsible for a particular disorder were identified by overlapping enlarged drawings of the individual scans at comparable brain-stem levels and identifying the areas where the abnormal MRI signals intersected. A statistical procedure was devised to exclude the possibility that the areas of overlap occurred by chance. In this paper, the findings in the group of patients with VI nerve palsy are reported since the location of their lesions could be predicted from known anatomy, so validating the procedure. The results were independently obtained with the overlapping technique and the statistical procedure and showed that the lesions were located in a region corresponding to the posterior part of the abducens fasciculus. This confirms that central lesions producing isolated lateral rectus weakness spare the abducens nuclei. The agreement between the procedures used and earlier clinical and experimental results suggest that the method we describe can be applied to locate the site of lesions on MRI scans in other groups of patients with more complex gaze disorders.

Abducens Nerve↗

Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II. Gaze palsy and internuclear ophthalmoplegia.

The site of lesions responsible for horizontal gaze palsy and various types of internuclear ophthalmoplegia (INO) was established by identifying the common areas where the abnormal MRI signals from patients with a given ocular-motor disorder overlapped. Patients with unilateral gaze palsy had lesions in the paramedian area of the pons, including the abducens nucleus, the lateral part of the nucleus reticularis pontis caudalis and the nucleus reticularis pontis oralis. Patients with abducens nucleus lesions showed additional clinical signs of lateral rectus weakness. Lesions responsible for bilateral gaze palsy involved the pontine tegmental raphe. Since this region contains the saccadic omnipause neurons, this finding suggests that damage to omnipause cells produces slowing of saccades rather than opsoclonus, as previously proposed. All INOs, regardless of the presence of impaired abduction or convergence, had similar MRI appearances. Frequently the lesions in patients with INO, were not confined to the medial longitudinal fasciculus (MLF) but also involved neighbouring structures at the pontine and mid-brain levels. There was a statistically significant association between the clinical severity of the INO and the presence of abnormal abduction or convergence. The findings suggest that the lesions outside the MLF, which may affect abducens, gaze or convergence pathways, are responsible for the presence of features additional to INO, depending on the magnitude of functional disruption they produce.

Abducens Nerve↗

A phase II trial of intraperitoneal cisplatin and etoposide for primary treatment of ovarian epithelial cancer.

We conducted a phase II trial of intraperitoneal (IP) cisplatin (DDP) and etoposide (VP-16) in stage III and IV newly diagnosed ovarian carcinoma patients with residual disease of any size. Twenty-three patients were entered, 19 had stage III and four stage IV disease. DDP 200 mg/m2 and VP-16 350 mg/m2 were given in 2 L saline IP via a Port-A-Cath (Pharmacia-Deltec, St Paul, MN). Sodium thiosulfate 4 g/m2 was given intravenously (IV) just before the start of IP instillation, and continued as a constant IV infusion of 2 g/m2/hr IV for a total of 6 hours. Treatment was given once every 4 weeks; six cycles of therapy were planned. Thirteen patients (56%) were in complete clinical remission at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125, and peritoneal cytology). Seven of these 13 underwent a second-look laparotomy: three (13%) were in pathologic complete remission and four (17%) had microscopic disease only. Projected survival is 68% at 27 months, with 10 patients being alive and continuously free of disease. There was a very rapid fall in mean CA-125 to within normal limits at the end of the second course of treatment. The major toxicity was myelosuppression with median nadir WBC, granulocyte, and platelet counts of 2,600, 896, and 205,000/microL, respectively. There was no cumulative renal damage, anemia, hypomagnesemia, or chemical peritonitis. Neurotoxicity was similar to that observed with IV dosing. We conclude that therapy with the IP DDP/VP-16/IV thiosulfate regimen, in which all cytotoxic drugs are given only by the IP route, produces less anemia and renal damage than standard IV DDP-containing regimens, and that survival with this regimen appears to be at least as good as that produced by IV programs.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of prostaglandin synthetase inhibitors on human preovulatory follicular fluid prostaglandin, thromboxane, and leukotriene concentrations.

This study evaluates the eicosanoid concentration in luteinized unruptured follicles (LUFs) on the ovaries of patients who had been treated with inhibitors of prostaglandin synthetase. Indomethacin, bromfenac, or azapropazone (or a placebo) was administered orally to 41 women during the periovulatory period. Follicular development was monitored by serial ultrasound examinations, and the onset of ovulation was regulated by an injection of hCG. Follicular fluid was aspirated during sterilization by minilaparotomy, which was performed just before the expected time of ovulation. Prostaglandin E2 and PGF2 alpha levels in the fluid were significantly reduced by indomethacin and bromfenac compared to those after placebo treatment. Bromfenac also reduced the follicular fluid leukotriene B4 level. Therefore, the development of luteinized unruptured follicles after treatment with nonsteroidal antiinflammatory drugs appears to be associated with a significant decrease in the synthesis of ovarian eicosanoids.

Adult↗

Bilateral congenital absence of the fibula.

The syndrome caused by congenital absence of the fibula has a number of pathologic abnormalities frequently associated with it, which are illustrated by the case reported. Postsurgical therapy on the involved extremity should take into account the patient's lack of joint motion within the tarsal region. With this in mind, special shoes or accommodative insoles, alone or in combination, should be prescribed in order to facilitate an increase in weightbearing activity with minimal discomfort.

Abnormalities, Multiple↗

Depression and neuropsychological test performance in acute spinal cord injury patients: lack of correlation.

Factors which have been causally related to neuropsychological deficits in acute spinal cord injury (SCI) patients include advanced age, limited educational level, acute traumatic brain injury, alcohol and/or substance abuse. Concomitant depression may impair motivation, prolong reaction time, and produce fatigue during neuropsychological testing, resulting in impaired performance. To test the hypothesis that abnormal neuropsychologic test results may be associated with depression, the Zung Self-Rating Depression Scale (ZUNG) and a comprehensive, predominantly motor-free neuropsychological test battery were administered to 66 acute SCI patients approximately 8 weeks following injury. Spinal cord injury groups were dichotomized based on their ZUNG scores. Comparison of neuropsychological test scores between SCI groups failed to demonstrate any impairment in neuropsychological performance, within the limits of the test battery administered, suggesting that cognitive performance in this sample of acute SCI patients may not be influenced by the presence of depression.

Journal Article↗

Rett's syndrome: a case study.

Rett's syndrome, first described in Austria in 1966 by Dr. Andreas Rett, became known as such in 1983 when Dr. Bengt Hagberg in Sweden realized that he and his colleagues from France and Portugal were not the first to recognize this disorder. In Sweden the syndrome was found to occur in at least 1 per 15,000 female births by 1985, about twice that of phenylketonuria (PKU) in the same area. The syndrome is limited to girls and involves atrophy of the brain with loss of previously learned cognitive and motor skills after eighteen months of age. Although there are variations in the numerous clinical features, most girls develop seizures, muscle wasting, contractures, severe weight loss and bizarre behaviors. All races are affected and four clinical stages have been established. Nurses are more likely to become involved during the final stage of this disorder when families can no longer cope without professional intervention. A case study of a 9 year-old girl is presented.

Female↗