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Biomedical subjects

A Hall

Publications and source records attributed to A Hall.

At least 289 records · Page 16Linked to original sources
PubMed1991

Purification and N-terminal sequence of the p21rho GTPase-activating protein, rho GAP.

Eukaryotic cells contain numerous small-molecular-mass GTP-binding proteins, but the processes that they regulate are not known. Different members of this protein family appear to be associated with specific GTPase-activating proteins (GAPs), and we have previously reported the identification of a cytoplasmic GAP (rho GAP) that stimulates the GTPase activity of p21rho but not of other small-molecular-mass GTP-binding proteins. We have now purified rho GAP 2000-fold from human spleen tissue using f.p.l.c. Electrotransfer of this 27.5 kDa protein on to an Immobilon-P transfer membrane followed by reconstitution of its enzymic activity confirmed its identity. Rho GAP was subjected to N-terminal sequence analysis and 15 amino acids were obtained. The sequence showed 53% identity with a region present in IRA1, a protein which stimulates the GTPase activity of RAS proteins in Saccharomyces cerevisiae. These results suggest that there is a family of sequence-related GAP proteins, which to date includes ras GAP and its yeast counterparts IRA1 and IRA2, rho GAP and the Neurofibromatosis gene product NF1.

Amino Acid Sequence↗
PubMed1991

Attendance of general practitioners at child protection case conferences.

OBJECTIVE: To investigate general practitioners' attendance at and views on child protection conferences and their confidence in dealing with sexual abuse in children. DESIGN: Anonymous postal questionnaire sent to all general practitioners in Tower Hamlets and review of consecutive case conferences held by social services for three months in 1989. SETTING: Tower Hamlets health district. SUBJECTS: 91 general practitioners, 56 of whom (62%) responded. MAIN OUTCOME MEASURES: Number of conferences attended, reasons for non-attendance, and reported confidence in dealing with sexual abuse. RESULTS: General practitioners estimated that 202 child protection conferences had been held in 1989 on their patients and that they had attended 85 of these. Information from social services for three months suggested that general practitioners had attended only nine of the 114 conferences reviewed. Timing of the conference was the most important reason for non-attendance. All respondents wanted access to the minutes of these conferences irrespective of their own attendance. Most general practitioners were very or moderately confident of their ability to detect child sexual abuse and non-accidental injury and to communicate with the family. CONCLUSION: More effort should be made to ensure that general practitioners are notified of case conferences and that the timing and location of conferences is compatible with their other commitments.

Attitude of Health Personnel↗
PubMed1991

Bcr encodes a GTPase-activating protein for p21rac.

More than thirty small guanine nucleotide-binding proteins related to the ras-encoded oncoprotein, termed Ras or p21ras, are known. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down-regulation of the active GTP-bound form. For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling. We have purified a GAP protein for p21rho, which is involved in the regulation of the actin cytoskeleton. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr (breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome-positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n-chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21rac. This result suggest that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia.

Amino Acid Sequence↗
PubMed1991

Mortality study of British pathologists.

Pathologists eligible for inclusion in the study were identified from the membership lists of the Royal College of Pathologists from 1974 to 1987, establishing a population of 4,512 members. Overall mortality was lower among the study group compared with the general population of England and Wales, although there were significantly more deaths due to suicide (observed 13, expected 4.9, SMR 265, 95% CI 141-454). Excess deaths due to cancer of the lymphatic and hemopoietic system were noted but they were not significantly increased. An excess of brain cancer death was marginally significant for male pathologists (observed 6, expected 2.5, SMR 240, 95% CI 88-522). Six of the 9 (66.7%) cases of all types of brain tumors reported in total were among hematologists, although this sub-specialty comprises approximately 16% of all pathologists.

Adult↗
PubMed1991

Prechronic inhalation toxicity studies of 2-mercaptobenzimidazole (2-MBI) in F344/N rats.

2-Mercaptobenzimidazole (2-MBI), used in rubber processing, is a suspect carcinogen structurally related to ethylene thiourea. The inhalation toxicity of 2-MBI was evaluated in male and female F344/N rats exposed 6 hr/day, 5 days/week to respirable aerosols generated by spray atomization of aqueous suspensions of the 2-MBI powder and subsequent drying of the resulting aerosols. Twelve exposures at target concentrations of 0, 6.3, 12.5, 25.0, 50.0, or 100 mg/m3 of 2-MBI produced a dose-related reduction in body weight gains, thyroid follicular cell hyperplasia, adrenal cortex fatty change, and pituitary atrophy. Sub-chronic exposures were conducted at target concentrations of 0, 3.1, 6.2, 12.5, 25.0, and 50.0 mg/m3 of 2-MBI. Rats at greater than or equal to 25 mg/m3 displayed hunched posture, hypoactivity, and reduced body weight gain, with compound related mortality at the highest exposure level. Anemia; increased SGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN, and cholesterol; and reduced free fatty acid were seen in rats at greater than or equal to 25 mg/m3. Increased thyroid weight and thyroid follicular cell hyperplasia were noted in both sexes at greater than or equal to 6.2 mg/m3, with reduced triiodothyronine and thyroxine levels in both sexes at greater than or equal to 12.5 mg/m3. Thyroid follicular cell hyperplasia was also seen in rats at 3.1 mg/m3. Thymus weights were significantly reduced in both sexes at all exposure levels with liver weight increases at greater than or equal to 6.2 mg/m3. Exposure-related histopathologic changes included pituitary cytoplasmic vacuolization, adrenal cortex necrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy, renal mineralization and tubular atrophy, and hypocellularity of the bone marrow.

Administration, Inhalation↗
PubMed1991

Eating disorder patient referrals from a population region 1977-1986.

Three hundred and forty-three eating disorder patients (50% anorexia nervosa, 37% bulimia and 13% atypical eating disorder) were seen by the eating disorder service in the Wellington (New Zealand) region between 1977 and 1986. Ninety-six per cent were female. Annual rate of referral for anorexia nervosa remained stable at 5 per 100,000 population (34 per 100,000 females aged 15-29 years). Annual referral rate for bulimia increased from 6 to 44 per 100,000 females aged 15-29 years.

Adolescent↗
PubMed1991

Co-stimulation of gastrointestinal tumour cell growth by gastrin, transforming growth factor alpha and insulin like growth factor-I.

Epidermal growth factor receptors and insulin like growth factor-I receptors were co-expressed on two gastric and three colorectal tumour cell lines. Previous studies have shown that gastrin receptors were also expressed at a low level or two of these cell lines. Both TGF alpha and IGF-I promoted cell growth in all of the cell lines tested. The cell doubling time of a colorectal cell line was reduced from 48 to 30-34 h. Furthermore the effects of the growth factors were additive. Each growth factor also increased the response of the cells to gastrin, but a combination of both growth factors and gastrin did not further increase growth.

Cell Division↗
PubMed1991

Enhanced expression of glutathione S-transferases in colorectal carcinoma compared to non-neoplastic mucosa.

Ten paired samples of primary human colorectal carcinoma and adjacent non-neoplastic mucosa were analysed for total glutathione S-transferase (GST) activities as determined by 1-chloro-2,4-dinitrobenzene assays. These tissues were also investigated for the expression of acidic (pi), basic (alpha) and neutral (mu) GSTs using Western blotting procedures and immunohistochemical staining. For each of the paired samples examined the total GST activity was higher in tumour than in adjacent non-neoplastic mucosa. Western blotting, using an antibody against acidic GST also showed strong immunoreactivity in all the samples with more intense reactions in tumour compared to mucosa in nine out of the ten paired samples. Low levels of basic GST were also expressed in all samples of tumour and mucosa. Neutral GST was not detectable in two samples of tumour and corresponding mucosa, but low levels of expression were demonstrated in the remaining eight. Immunohistochemical staining for acidic GST showed a dark brown reaction in all tumour cells; in non-neoplastic mucosa there was positive immunoreactivity for epithelial cells situated deep within the crypts and a negative reaction for surface epithelial cells. Immunohistochemical staining for basic GST was negative except for one sample of tumour and two of mucosa. Neutral GST was expressed only in two samples of tumour and two samples of mucosa. We therefore conclude that there is enhanced expression of GSTs, acidic GST being the predominant form, in tumour compared to normal mucosa, in keeping with a role for GSTs in colonic carcinogenesis and acquired or innate drug resistance.

Blotting, Western↗
PubMed1991

Psychosocial and sexual impact of diagnosis and treatment of breast cancer.

Psychosocial and sexual disturbances are common sequelae to a diagnosis of breast cancer and its treatment. The intuitively plausible hope that the advent of breast conserving techniques would prevent the psychological distress experienced following mastectomy has not been realised. Studies comparing psychosocial outcome of mastectomy with lumpectomy and radiotherapy reveal some advantage to women treated with breast conserving procedures in terms of body image, but very little difference in terms of psychiatric morbidity or sexual dysfunction. Whatever the primary therapy, women must still confront the fact that they have had cancer, a life-threatening disease which may recur. In this chapter the research comparing psychological outcome between mastectomy and lumpectomy is critically reviewed and the implications that these data have for clinical practice are discussed.

Adaptation, Psychological↗
PubMed1991

Antibody response to pneumococcal capsular polysaccharide vaccine in African children.

Antibody titers to six pneumococcal polysaccharides were measured by enzyme-linked immunosorbent assay in Gambian children before and 1 month after vaccination with a 23-valent pneumococcal capsular polysaccharide vaccine at the ages of 2, 4, 6 or 9 months or at 5 to 10 years of age. IgG responses to type 1, 3 and 5 polysaccharides were seen in children in all age groups. Responses to type 19F and 23F polysaccharides were seen only in the oldest children. Few children of any age responded to immunization with type 6A pneumococcal polysaccharide. The immune response of Gambian infants to immunization with six components of a polyvalent pneumococcal polysaccharide vaccine was comparable with that described previously in Finnish infants and would be unlikely to provide substantial protection against invasive pneumococcal disease.

Antibodies, Bacterial↗
PubMed1991

The prevalence of eating disorders in recently admitted psychiatric in-patients.

Of 107 recently admitted psychiatric patients screened for eating-disorder symptoms by questionnaire, 17% met DSM-III-R criteria for eating disorders. Eight patients (one male) had bulimia nervosa. Ten patients had eating disorder not otherwise specified: seven (three male) bulimic type, and three (one male) anorexia nervosa type. The most common concurrent diagnoses were mood and personality disorders. As eating-disorder symptoms are relevant to the diagnosis and management of other psychiatric disorders they should be assessed routinely in all psychiatric patients.

Adolescent↗
PubMed1991

Albendazole and infections with Trichuris trichiura and Giardia intestinalis.

One hundred and twenty-eight children aged 4 to 11 years old in Dhaka, Bangladesh were treated for infections with Trichuris trichiura and other intestinal parasites using a single dose of 400 mg of albendazole. Only one Trichuris infection was apparently cured although egg counts fell by about 50%. A larger single dosage is recommended to treat Trichuris. Eleven out of 46 infections with Giardia intestinalis were not detected after treatment (p less than 0.001).

Albendazole↗
PubMed1990

Morphological alterations of Xenopus oocytes induced by valine-14 p21rho depend on isoprenylation and are inhibited by Clostridium botulinum C3 ADP-ribosyltransferase.

Microinjection of the constitutively active recombinant Val-14 p21rho A into Xenopus oocytes induced dramatic morphological changes with redistribution of pigments from the animal pole resulting in spotted oocytes. The effects induced by Val-14 p21rho A were regulated by progesterone in a dose-dependent manner whereas prior ADP-ribosylation of the rho protein blocked its activity. About 30 min after microinjection, p21 rho was associated with the plasma membrane. The membrane association of p21rho and its biological activity were inhibited by lovastatin, an inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase. The findings suggest that membrane attachment and biological activity of p21rho depend on isoprenylation of the GTP-binding protein.

ADP Ribose Transferases↗
PubMed1990

Interaction of recombinant rho A GTP-binding proteins with photoexcited rhodopsin.

The small molecular mass GTP-binding proteins rho A, B and C are targets for ADP-ribosyltransferase activity of the botulinum exoenzyme C3. The possible interaction of recombinant rho A proteins expressed in E. coli with photoexcited rhodopsin was studied by reconstitution with bovine rod outer segment (ROS) membranes depleted of endogenous GTP-binding proteins by treatment with urea. As reported for C3 substrates present in untreated ROS membranes, ADP-ribosylation of recombinant rho A proteins, both normal and Val-14 mutant, by C3 was inhibited when reconstituted with illuminated compared to dark-adapted ROS membranes pretreated with urea. GDP reduced the light-induced inhibition, while GTP[S] and light inhibited ADP-ribosylation of rho A proteins in a synergistic manner.

Adenosine Diphosphate Ribose↗
PubMed1990

Is the prevalence of bulimia nervosa higher among tertiary education populations?

In this study the prevalence of bulimia nervosa was estimated among 243 women in a tertiary educational setting. The results showed 43.6% (95% CI, 37.4 to 49.8) to report binge eating, the cardinal feature of bulimia nervosa, at some stage in the past and 2.5% (95% CI, 1.0 to 5.6) the full criteria for current bulimia nervosa. These figures are significantly higher than those reported recently for a general population sample in the same age range. Despite methodological differences between the two surveys the results give some support to claims that women in these settings are at a greater risk of developing eating disorders.

Adult↗
PubMed1990

Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial.

OBJECTIVES: To assess outside a clinical trial the psychological outcome of different treatment policies in women with early breast cancer who underwent either mastectomy or breast conservation surgery depending on the surgeon's opinion or the patient's choice. To determine whether the extent of psychiatric morbidity reported in women who underwent breast conservation surgery was associated with their participation in a randomised clinical trial. DESIGN: Prospective, multicentre study capitalising on individual and motivational differences among patients and the different management policies among surgeons for treating patients with early breast cancer. SETTING: 12 District general hospitals, three London teaching hospitals, and four private hospitals. PATIENTS: 269 Women under 75 with a probable diagnosis of stage I or II breast cancer who were referred to 22 different surgeons. INTERVENTIONS: Surgery and radiotherapy or adjuvant chemotherapy, or both, depending on the individual surgeon's stated preferences for managing early breast cancer. MAIN OUTCOME MEASURES: Anxiety and depression as assessed by standard methods two weeks, three months, and 12 months after surgery. RESULTS: Of the 269 women, 31 were treated by surgeons who favoured mastectomy, 120 by surgeons who favoured breast conservation, and 118 by surgeons who offered a choice of treatment. Sixty two of the women treated by surgeons who offered a choice were eligible to choose their surgery, and 43 of these chose breast conserving surgery. The incidences of anxiety, depression, and sexual dysfunction were high in all treatment groups. There were no significant differences in the incidences of anxiety and depression between women who underwent mastectomy and those who underwent lumpectomy. A significant effect of surgeon type on the incidence of depression was observed, with patients treated by surgeons who offered a choice showing less depression than those treated by other surgeons (p = 0.06). There was no significant difference in psychiatric morbidity between women treated by surgeons who offered a choice who were eligible to choose their treatment and those in the same group who were not able to choose. Most of the women (159/244) gave fear of cancer as their primary fear rather than fear of losing a breast. The overall incidences of psychiatric morbidity in women who underwent mastectomy and those who underwent lumpectomy were similar to those found in the Cancer Research Campaign breast conservation study. At 12 months 28% of women who underwent mastectomy in the present study were anxious compared with 26% in the earlier study, and 27% of women in the present study who underwent lumpectomy were anxious compared with 31% in the earlier study. In both the present and earlier study 21% of women who underwent mastectomy were depressed, and 19% of women who underwent lumpectomy in the present study were depressed compared with 27% in the earlier study.) CONCLUSIONS: There is still no evidence that women with early breast cancer who undergo breast conservation surgery have less psychiatric morbidity after treatment than those who undergo mastectomy. Women who surrender autonomy for decision making by agreeing to participate in randomised clinical trials do not experience any different psychological, sexual, or social problems from those women who are treated for breast cancer outside a clinical trial.

Adult↗