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N R Hall

Publications and source records attributed to N R Hall.

At least 19 recordsLinked to original sources
PubMed1996

Hereditary susceptibility to colorectal cancer. Relatives of early onset cases are particularly at risk.

Close relatives of patients with colorectal cancer are at an increased risk of developing a colorectal malignancy themselves. PURPOSE. A study was conducted to compare risks in relatives of patients diagnosed at different ages. METHODS. Family histories were taken from two cohorts of patients with colorectal cancer: Group A, a population group of 65 patients diagnosed at or under 45 (median, 42) years; Group B, 212 patients of all ages (median, 68 years) treated in a single surgeon's practice. RESULTS. Overall relative risk of colorectal cancer in first-degree relatives was 5.2 in Group A and 2.3 in Group B. There was familial clustering of colorectal cancers suggestive of hereditary nonpolyposis colorectal cancer in 13 (20 percent) families in Group A but in only 3 (1.5 percent) families in the second group. Cumulative incidence of colorectal cancer for relatives of the young cohort rose steeply from 40 years, reaching 5 percent at age 50 years and 10 percent at age 70 years. This contrasts with risk for relatives of older patients, in whom the shape of the curve resembles that of the overall population risk, reaching 5 percent at age 70 years and 10 percent at age 80 years. CONCLUSIONS. There appears to be a quantitative and qualitative increase in risk to relatives of patients diagnosed at a young age compared with those diagnosed later in life, at least part of which is likely to be the result of a hereditary susceptibility. Close relatives of early onset cases warrant more intensive endoscopic screening and at an earlier age than relatives of patients diagnosed at older ages.

Adult↗
PubMed1996

The effects of interleukin-1 receptor antagonist protein (IRAP) infusion following spinal cord transection in rats.

A laminectomy was performed at the T5-T6 vertebral level in adult, male, Sprague-Dawley rats and the spinal cord transected with a scalpel. A group of sham animals was subjected to the same surgery without the transection step. A group of unhandled control rats was also included. A subgroup of transected animals received a subcutaneous osmotic minipump that dispensed IL-1 receptor antagonist protein (IRAP) at the transection site for 7 consecutive days. Another transected subgroup received a minipump that infused the vehicle only. IRAP-treated rats displayed a significant reduction in body temperature (p < 0.05) compared with vehicle-treated rats. The IRAP-treated rats were also less active when assessed for locomotor behavior using an HVS computerized tracking system (p < 0.01). IRAP treatment had no effect on serum corticosterone, beta-endorphin levels, Con A, PHA, or LPS-induced splenocyte mitogenesis when compared with vehicle-treated animals. However, half of the IRAP-treated animals exhibited a substantive reduction in the number of reactive astrocytes near the transection site, suggesting a possible effect of IRAP on astrocyte activation.

Animals↗
PubMed1996

Psychological disturbance alters thymic and adrenal hormone secretion in a parallel but independent manner.

Thymosin-alpha 1 (thymosin alpha 1) and cortisol levels were evaluated in juvenile squirrel monkeys to investigate the influence of psychological disturbance on thymic and adrenal hormone activity. Hormone levels were assessed in peripheral circulation following removal of monkeys from their social group to establish the time course of thymosin and cortisol alterations. Thymosin alpha 1 was significantly decreased after social separation in association with increased adrenocortical activity, especially during the first day after being housed alone. The temporal pattern suggested that both hormone systems are involved in the acute inhibition of functional immunity observed following this type of psychological disturbance. A second study verified that the decrement in thymosin alpha 1 levels was replicable and also sensitive to psychosocial factors that influence the level of induced disturbance. In addition, changes in thymosin secretion could be attenuated partially by pharmacological inhibition of the cortisol response and opiate hormone action. Nevertheless, the decrease in thymosin alpha 1 secretion did not appear to be a secondary consequence of adrenocortical secretion, and instead probably emanates from a general shift in neuroendocrine activity.

Animals↗
PubMed1995

Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations.

Hereditary nonpolyposis colorectal carcinoma is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in at least four genes such as hMSH2, hMLH1, hPMS1, and hPMS2 which encode components of a DNA mismatch repair system. The hMLH1 genomic locus on chromosome 3p has been cloned and shown to cover approximately 58 kilobases of genomic DNA and contain 19 exons. The sequence of all of the intron-exon junctions has been determined and used to develop methods for analyzing each hMLH1 exon for mutations. Using these methods to analyze a 3p-linked hereditary nonpolyposis colorectal carcinoma kindred, we have demonstrated that cancer susceptibility in this family is due to the inheritance of a frame shift mutation in the hMLH1 gene.

Base Sequence↗
PubMed1995

High tie of the inferior mesenteric artery in distal colorectal resections--a safe vascular procedure.

Division of the inferior mesenteric artery flush with the aorta (high tie) allows a tension-free anastomosis in distal colorectal resections but may also diminish the blood supply. Tissue oxygen tension was measured proximal to the resection margin before and after either low or high division of the inferior mesenteric artery in 62 patients undergoing elective colorectal resections. Oxygenation was maintained or improved when the transverse (median change after vs before resection for low tie +9 mmHg (P < 0.05), high tie +8 mmHg (P = 0.3)) and descending colon (low tie +7 mmHg (p < 0.01), high tie +1 mmHg (p = 0.67)) were used for the anastomosis but diminished for sigmoid anastomoses (low tie -4 mmHg (P = 0.42), high tie -9 mmHg (P < 0.05)). Change in oxygenation was significantly affected by location of proximal resection site but not by choice of high or low tie. These results suggest that the marginal artery provides a more than adequate vascular supply to the transverse and descending colon, but that the sigmoid colon is not suitable for anastomosis. We conclude that the sigmoid colon be sacrificed and there should be no hesitation in performing a high tie to avoid tension in low pelvic anastomoses.

Aged↗
PubMed1994

Genetic susceptibility to colorectal cancer in patients under 45 years of age.

A study was conducted to assess the genetic contribution to the development of colorectal cancer in young probands. Of 83 patients aged 45 years or under diagnosed with colorectal cancer in one health region over a 2-year period, 65 or their surviving next of kin were available for interview, from whom were obtained 60 detailed and five limited family histories. Five families fulfilled the Amsterdam criteria and a further eight satisfied less strict criteria for hereditary non-polyposis colorectal cancer, a total of 20 per cent of the cohort. Eleven of these families came from the subgroup of 13 probands who had one or more first-degree relatives with colorectal cancer. Overall the relative risk of colorectal cancer in close relatives was 5.2 (P < 0.0001). This risk was highest for female relatives at 9.7 (P < 0.0001) and relatives of female probands at 6.7 (P < 0.0001). This study highlights the importance of taking a family history in this group of patients. Screening by colonoscopy for all close relatives of young patients with colorectal cancer is recommended.

Adult↗
PubMed1994

Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of genomic DNA and to contain 16 exons. The sequence of all the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family.

Amino Acid Sequence↗
PubMed1994

Intron splice acceptor site sequence variation in the hereditary non-polyposis colorectal cancer gene hMSH2.

Common but weakly penetrant mutations of certain genes may confer an increased susceptibility to colorectal cancer and account for a proportion of 'sporadic' cases. We analysed DNA from 111 colorectal cancer cases and 114 controls for a specific candidate sequence variation in the hereditary non-polyposis colorectal cancer gene hMSH2. The variant sequence was found in a quarter of individuals, and there was no difference between cancer cases and controls, according to age of development of cancer or presence of family history. It thus appears that this particular sequence variation is a polymorphism rather than a mutation which increases cancer susceptibility.

Adolescent↗
PubMed1994

Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer family syndrome.

The Muir-Torre syndrome, in which sebaceous gland tumours occur in association with internal malignancy, is inherited as an autosomal dominant disorder. Many features of the syndrome are similar to those of the Lynch II cancer family syndrome, and thus the two disorders might share a common genetic basis. We typed two large families with DNA markers on chromosome 2p around D2S123, a site recently shown to be linked to the Lynch II syndrome. LOD scores at this locus demonstrated significant and tight linkage to D2S123, suggesting that defects in the same gene might give rise to both syndromes.

Adult↗
PubMed1994

The role of CA-242 and CEA in surveillance following curative resection for colorectal cancer.

This study was undertaken to evaluate the role of a new tumour marker, CA-242, alone or in combination with CEA in the practical management of colorectal cancer patients after potentially curative resection. A cohort of 149 patients who had undergone 'curative' surgery was followed up according to an intensive protocol in order to detect recurrent disease. Over a median tumour marker follow-up period of 24 months there were 25 recurrences in 24 patients. Both CEA and CA-242 alone detected half the local recurrences. The sensitivity of CEA was 84% for distant or mixed recurrence compared with 64% for CA-242. An abnormality of either CEA or CA-242 enabled detection of five out of six local recurrences and 17 out of 19 distant or mixed recurrences with a median lead time of 5 months for each marker. Both markers were elevated concurrently in only one local and 11 distant recurrences. While CA-242 alone is not superior to CEA, their combined use (either abnormal) has a high sensitivity (88%), specificity (78%) and negative predictive value (97%); this may be useful in reducing unnecessary investigations in follow-up programmes and as a guide to the initiation of further treatment for recurrent disease.

Adult↗
PubMed1994

Muir-Torre syndrome: a variant of the cancer family syndrome.

Muir-Torre syndrome is characterised by the association of sebaceous tumours of the skin with internal malignancy. In many instances there is a strong family history of cancer and the autosomal dominant mode of inheritance, tumour spectrum, and high incidence of synchronous and metachronous tumours show parallels with the cancer family syndrome or Lynch II syndrome. We report a five generation family with at least two persons displaying the Muir-Torre phenotype, while many other family members have had tumours consistent with cancer family syndrome. The majority of tumours are gastrointestinal, gynaecological, and urological, with several persons having multiple primaries. The prognosis appears to be better than would be expected. Sebaceous tumours are a marker for internal malignancy and should prompt a search for occult cancer in the individual person and family members. In documented Muir-Torre families, at risk persons should be entered into screening programmes similar to those used in the Lynch II syndrome.

Adult↗
PubMed1993

Immunological responses of breast cancer patients to behavioral interventions.

This article reports the results of an 18-month study of immune system and psychological changes in stage 1 breast cancer patients provided with relaxation, guided imagery, and biofeedback training. Thirteen lymph node negative patients who had recovered from a modified radical mastectomy were randomly assigned to either an immediate treatment or a delayed treatment control group. Multiple pre-post psychological measures were performed. Significant effects were found in natural killer cell (NK) activity (p < .017), mixed lymphocyte responsiveness (MLR) (p < .001), concanavalin A (Con-A) responsiveness (p < .001), and the number of peripheral blood lymphocytes (PBL) (p < .01). No significant psychological changes were detected; however, reductions were seen in psychological inventory scales measuring anxiety. The results show that behavioral interventions can be correlated with immune system measures, thereby replicating the results of an earlier pilot study from our Center. Discussion is provided on differential T-cell and B-cell responsiveness to behavioral interventions.

Adult↗
PubMed1993

Interleukin-1 beta stimulates adrenocorticotropin and corticosterone release in 10-day-old rat pups.

Interleukin-1 (IL-1) is a cytokine secreted in response to immunological challenge which has effects in many physiological systems in adult models. Among the central nervous system effects of IL-1 are its ability to alter sleep patterns, body temperature, and certain neuroendocrine parameters including the release of ACTH and corticosterone (B) in vivo. This study investigated the ability of IL-1 to induce ACTH and B release in 10-day-old rats. This age was chosen due to a well documented phenomenon, the stress hyporesponsive period (SHRP), in which rodents display a blunted pituitary-adrenal response to stressors during the first 2 postnatal weeks (postnatal days 3-14). Administration of IL-1 to rat pups during the SHRP resulted in robust ACTH and B increases. Data are discussed in terms of the site of action and ontogeny of negative feedback mechanisms in the hypothalamic-pituitary-adrenal axis.

Adrenal Cortex↗
PubMed1992

Effects of exercise on immune functions of undernourished mice.

Regular moderate exercise may modulate the response to a stressor and thus improve immune functions in conditions commonly associated with immunodepression and elevated levels of stress hormones. For example, anorexia nervosa patients, many of whom engage in regular aerobic exercise, generally have normal immune function and viral disease resistance in spite of their severe undernutrition. To test the hypothesis that exercise can prevent undernutrition-induced immunodepression, mice were fed a nutritionally complete, semi-purified diet, either ad libitum or in restricted quantities to induce 25% loss of initial weight over 3 weeks. Half the animals from each dietary group were run on a treadmill for 30 min/day, 5 days/week. Exercise had no effect on several measures of nutritional status. Spleen weight and blastogenic response to lipopolysaccharide were significantly increased by exercise in undernourished mice. In vivo antibody response to sheep red blood cells, and in vitro splenic responses to concanavalin A and phytohemagglutin were not significantly affected by exercise. Serum corticosterone level was increased by food restriction and significantly decreased by exercise in the undernourished mice. Within a treatment group there were no significant correlations between serum corticosterone level and any immune system measure. Hypothalamic concentration of uric acid was increased in food restriction groups and concentration of norepinephrine was increased in exercise groups. The results suggest that regular exercise may help prevent undernutrition-induced immunodepression, possibly through modulation of the stress response.

Analysis of Variance↗
PubMed1992

Human recombinant interferon alpha inhibits naloxone binding to rat brain membranes.

Regulation of certain central nervous system (CNS) functions by the immune system may involve interferons (IFNs) acting through opioid receptors. Human recombinant interferon alpha (hrIFN alpha), as well as natural IFN alpha, have been reported to modulate a variety of physiological CNS functions both in vivo and in vitro. If the mechanism is via opioid receptors then IFN alpha should inhibit the binding of certain opioid radioligands to brain membranes. This study reports the inhibitory effect of hrIFN alpha on the binding of 3H-naloxone to rat brain membranes in vitro. The inhibitory effect at 37 degrees C is hrIFN alpha concentration dependent over the range of 500 to 6000 antiviral units per ml (U/ml) with 500 micrograms of membrane protein. The presence of NaCl (100mM) increases specific binding of naloxone and attenuates the inhibitory effect of hrIFN alpha. The inhibitory effect of hrIFN alpha is sensitive to temperature with maximum inhibition observed at 37 degrees C, and less as incubation temperature is reduced. These data suggest that IFN alpha may modulate certain physiologic functions via opioid pathways in the brain.

Animals↗
PubMed1992

Thymic regulation of the hypothalamic-pituitary-gonadal axis.

The thymus gland and the cells that it regulates produce a number of soluble factors that are capable of indirectly modulating the immune system via reproductive neuroendocrine circuits. Studies dating to the turn of the century were designed to evaluate the effects of partially purified thymic extracts in treating various reproductive disorders as well as changes in gonadal tissue weights. More recent studies have focused on the chemical nature of the factors responsible for regulating reproductive function. A number of factors have been described. These include thymosin beta 4 which has been found to stimulate the release of luteinizing hormone releasing hormone and luteinizing hormone (LH). Other factors such as interleukin-1 (IL-1) have been found to inhibit the release of these two peptides. IL-1 has also been found to alter the expression of LH receptors in rat granulosa cells. Certain interferons have been found capable of suppressing estrogen and progesterone release. While many of the studies have been carried out using adult animal models, there is increasing evidence that exposure to cytokines during early development can have long lasting if not permanent effects upon the reproductive axis. These and related topics are the subject of this review.

Animals↗