Search PubMed⌕ Search

Biomedical subjects

J Ho

Publications and source records attributed to J Ho.

At least 55 records · Page 3Linked to original sources

Chinese mothers intention to breastfeed, actual achievement and early postnatal experience.

Thirty Chinese primiparous mothers were asked during the antenatal period their breastfeeding intention and then interviewed at delivery and 6 weeks post delivery. One mother had no intention to breastfeed. Ten mothers intended exclusive breastfeeding for one month and 19 for 6 weeks or more. At 6 weeks post delivery only 4 mothers were still breastfeeding. A total of 22 (73%) did not achieve their initial intention. For any future pregnancy, 5 chose exclusive breastfeeding, 22 complementary and 3 formula feeding. Chinese primiparous mothers have high breastfeeding intentions but the majority do not achieve them and their experience has discouraged them from exclusive breastfeeding in future pregnancies.

Asian People↗

The COOH-terminal domain of Myo2p, a yeast myosin V, has a direct role in secretory vesicle targeting.

MYO2 encodes a type V myosin heavy chain needed for the targeting of vacuoles and secretory vesicles to the growing bud of yeast. Here we describe new myo2 alleles containing conditional lethal mutations in the COOH-terminal tail domain. Within 5 min of shifting to the restrictive temperature, the polarized distribution of secretory vesicles is abolished without affecting the distribution of actin or the mutant Myo2p, showing that the tail has a direct role in vesicle targeting. We also show that the actin cable-dependent translocation of Myo2p to growth sites does not require secretory vesicle cargo. Although a fusion protein containing the Myo2p tail also concentrates at growth sites, this accumulation depends on the polarized delivery of secretory vesicles, implying that the Myo2p tail binds to secretory vesicles. Most of the new mutations alter a region of the Myo2p tail conserved with vertebrate myosin Vs but divergent from Myo4p, the myosin V involved in mRNA transport, and genetic data suggest that the tail interacts with Smy1p, a kinesin homologue, and Sec4p, a vesicle-associated Rab protein. The data support a model in which the Myo2p tail tethers secretory vesicles, and the motor transports them down polarized actin cables to the site of exocytosis.

Alleles↗

Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome. Genes Chromosomes Cancer 25:75-81, 1999.

Chan TL, Yuen ST, Chung LP, Ho JWC, Kwan K, Fan YW, Chan ASY, Leung SY. 1999. Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome. Genes Chromosomes Cancer 25:75-81, 1999. It has come to our attention that the three patients described in the article above, were also included in a report by Leung et al., American Journal of Pathology, 153:1181-1189, 1998. Reference to the American Journal of Pathology article was inadvertently omitted

Journal Article↗

A real time quantitative PCR-based method for the detection and quantification of simian virus 40.

A real time quantitative PCR-based simian virus 40 (SV40) detection and quantification method has been developed. This method takes advantage of the 5' to 3'-exonuclease activity of Taq DNA polymerase and utilizes the PRISM 7700 sequence detection system of PE Applied Biosystems for direct monitoring of PCR product accumulation through a dual-labelled fluorogenic probe. This method provides accurate, precise and reproducible quantification of SV40 DNA over a linear dynamic range of at least 100,000-fold with a minimum detection level of 6.4 copy equivalents/microL of SV40 viral particle in test samples. The sample preparation procedure employed allows for efficient and consistent recovery of SV40 DNA from test samples. High concentrations of protein and cellular DNA presenting in test samples have been demonstrated to have no impact on SV40 quantification. This method offers significant advantages over other PCR methods and cell-based infectivity assays currently available for SV40 detection and quantification. The availability of this method should greatly facilitate the pathogenic investigation of SV40, as well as viral clearance evaluations required for the development of new biological products.

DNA, Viral↗

Triple therapy for Helicobacter pylori eradication is more effective than long-term maintenance antisecretory treatment in the prevention of recurrence of duodenal ulcer: a prospective long-term follow-up study.

BACKGROUND: The effectiveness of Helicobacter pylori eradication treatment and long term acid suppression maintenance in the natural course of duodenal ulcer has not been directly compared. AIM: To compare in a prospective randomized study the effectiveness of H. pylori eradication on the prevention of recurrence of duodenal ulcer with long-term maintenance acid suppression therapy. METHODS: One hundred and fourteen duodenal ulcer patients were randomized to the treatment over a 12-month period. Fifty-seven of them received triple therapy consisting of 1 g sucralfate q.d.s. for 28 days, 300 mg metronidazole q.d.s. for 14 days and 250 mg clarithromycin q.d.s. for 14 days. Another 57 received 20 mg omeprazole q.d.s. for 12 months. An upper endoscopy was performed before treatment, at 6 weeks, and 2, 6 and 12 months after the first endoscopy. Side-effects were self-recorded and clinical follow-ups were arranged for up to 4.25 years. RESULTS: The ulcer healing rate was 90.2% (95% confidence interval (95% CI): 79-97%) in the omeprazole group at 6 weeks as compared to 83.3% (95% CI: 70-93%) in the triple therapy group (P = 0.38). There was a higher success rate of pain control in the omeprazole group. Side-effects were more frequently reported and compliance was poorer in the triple therapy group during the first 4 weeks. During follow-up, more relapses were seen in the omeprazole group (9.8%, 95% CI: 3-21%) than the triple therapy group (4.2%, 95% CI: 1-13%) at 1 year (P = 0.44). All relapses were due to the persistence of H. pylori infection. At the 1 year follow-up, none of the patients who were H. pylori negative had an endoscopic relapse compared to 7 out of 56 patients who remained H. pylori positive (12.5%, 95% CI: 5-24%, P = 0.018). After a mean follow-up of 4.07 years, none of those who remained H. pylori negative had an ulcer relapse while the 11 out of 41 who remained H. pylori positive had an ulcer relapse (26.8%, 95% CI 14-43, P = 0. 0005). CONCLUSIONS: Both regimens were highly effective in healing ulcers. The eradication of H. pylori infection was associated with more side-effects and poor compliance but was more effective than the maintenance therapy in reducing the recurrence of duodenal ulcers. For the prevention of ulcer recurrence, testing of H. pylori status after triple therapy is more important than maintenance therapy.

Adult↗

Seroprevalence of cytotoxin-associated gene A positive Helicobacter pylori strains in Changle, an area with very high prevalence of gastric cancer in south China.

BACKGROUND: Helicobacter pylori, especially the CagA-positive strains, are closely associated with peptic ulcers and gastric cancers. We performed a large scale gastric cancer screening project and examined the prevalence of H. pylori and CagA-positive strains in Changle, China, an area with one of the World's highest gastric cancer mortality. We also compared the prevalence with that in Hong Kong which has one-tenth of the gastric cancer mortality of that in Changle. METHODS: A total of 2424 subjects in Changle and 523 subjects in Hong Kong had endoscopic examination and venesection. Sera were tested for anti-H. pylori antibody and anti-CagA antibody and correlated with endoscopic findings. RESULTS: In Changle, 80. 9% of the subjects were H. pylori carriers. Out of 551 carriers, 408 (74%) were positive for anti-CagA antibody. A total of 76% and 87% of the asymptomatic and gastric cancer patients were positive for anti-CagA antibody, respectively (P > 0.05). Compared to Hong Kong, there was a significantly (P < 0.0001) higher prevalence of CagA-positive strains in asymptomatic subjects in Changle (76%) than in Hong Kong (28%), but not in peptic ulcers or gastric cancers. CONCLUSIONS: Subjects in Changle had a high prevalence of H. pylori infection and a high prevalence of the CagA-positive strains. The contrast in the prevalence of CagA-positive strains, in asymptomatic subjects in two areas with differing gastric cancer mortality, supports the pathogenic role of CagA-positive strains in gastric carcinogenesis.

Adolescent↗

Differential Helicobacter pylori infection rates in two contrasting gastric cancer risk regions of South China. China Gastric Cancer Study Group.

BACKGROUND: Carriers of Helicobacter pylori are believed to have a three- to six-fold increased risk of developing gastric cancer. We have recently conducted a simultaneous cross-sectional population study on the prevalence of H. pylori infection in a cohort of asymptomatic adult volunteers in two contrasting gastric cancer risk regions of South China, Hong Kong and Changle of Fujian. Their mean annual gastric cancer mortality has been approximately 7.5 and 75/100 000 population, respectively, since the beginning of the last decade. The aim of this study was to evaluate if H. pylori prevalence bears any relationship to gastric cancer mortality rates in these two southern regions of China. METHODS: Sera were obtained from 397 volunteers in Hong Kong. They were tested for anti-H.pylori immunoglobulin (Ig) G antibody by using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Volunteers of Changle (1456) had upper endoscopy examination and were also tested for anti-H. pylori IgG antibody by the same ELISA method. RESULTS: The overall H. pylori infection prevalence was significantly higher in Changle (80.4%) than in Hong Kong (58.4%; P< 0.01). The high prevalence is associated with more atrophic gastritis. The overall risk of gastric cancer in people of Changle is approximately five-fold that of Hong Kong (adjusted odds ratio 4.9, 95% CI 2.5-9.8). CONCLUSIONS: It is concluded that the prevalence of H. pylori infection rates bear a direct relationship to gastric cancer mortality rates in these two southern regions of China. Thus, H. pylori most likely plays a significant aetiopathogenetic role in gastric carcinogenesis in subjects living in Changle.

Adult↗

The accuracy of the TriTrac-R3D accelerometer to estimate energy expenditure.

PURPOSE: This study examined the reliability and validity of the TriTrac-R3D triaxial accelerometer to estimate energy expenditure during various modes of exercise. METHODS: Twenty subjects (age = 21.5+/-3.4 yr; body mass index = 23.3+/-3.6 kg x m(-2)) performed five exercises (treadmill walking, treadmill running, stepping, stationary cycling, and slideboard), with each lasting 20-30 min and workload increased at 10-min intervals. To test the inter-TriTrac reliability, two TriTrac-R3D accelerometers were worn during each exercise period, and to examine validity, a simultaneous measurement of energy expenditure was made using indirect calorimetry (SensorMedics 2900 Metabolic Cart). RESULTS: Results showed a significant correlation between the two TriTrac-R3D accelerometers during all exercises. The difference in estimated energy expenditure between the two accelerometers during the walking, stepping, and slideboard exercises was less than 1 kcal x min(-1) but statistically significant (P<0.05). There was also a significant correlation between energy expenditure estimated by each of the TriTrac-R3D accelerometers and indirect calorimetry during walking, running, stepping, and slideboard exercise (P<0.05). The interaction of Method x Workload was significant (P<0.05) for each exercise, indicating that the TriTrac-R3D underestimates energy expenditure and that the magnitude of this underestimation increases as workload increases. CONCLUSIONS: Therefore, energy expenditure estimated via triaxial accelerometry does not increase with increasing workloads. These results suggest that there are limitations to using triaxial accelerometry to quantify energy expenditure.

Adolescent↗

Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer.

PURPOSE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, but data for small-cell lung cancer (SCLC) are lacking. The aim of this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative to standard prognostic factors. PATIENTS AND METHODS: Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization was used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival. RESULTS: Samples from 46 patients were evaluated: 30 males, 16 females; 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells. Stromal staining of TIMP-1 to -3 was present in less than 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P =.043). Significant factors for survival were tumor stage (P =.0021); weight loss (P =. 013); and high tumor cell expression of MMP-3 (P =.077), MMP-11 (P =. 031), and MMP-14 (P =.019). MMP and TIMP expression did not differ significantly between stages. CONCLUSION: MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC.

Carcinoma, Small Cell↗

An office-based intervention to maintain parent-adolescent teamwork in diabetes management. Impact on parent involvement, family conflict, and subsequent glycemic control.

OBJECTIVE: To design and evaluate an office-based intervention aimed at maintaining parent-adolescent teamwork in diabetes management tasks without increasing diabetes-related family conflict. RESEARCH DESIGN AND METHODS: There were 85 patients (aged 10-15 years, mean 12.6 years) with type 1 diabetes (mean duration 5.5 years; mean HbA1c 8.5%) who were randomly assigned to one of three study groups--teamwork, attention control, and standard care--and followed for 24 months. At each visit, parent involvement in insulin administration and blood glucose monitoring was assessed. The teamwork and attention control interventions were integrated into routine ambulatory visits over the first 12 months (four medical visits). Measures of diabetes-related family conflict were collected at baseline and after 12 months. All patients were followed for an additional 12 months with respect to glycemic control. RESULTS: In the teamwork group, there was no major deterioration (0%) in parent involvement in insulin administration, in contrast to 16% major deterioration in the combined comparison (attention control and standard care) group (P < 0.03). Similarly, no teamwork families showed major deterioration in parent involvement with blood glucose monitoring versus 11% in the comparison group (P < 0.07). On both the Diabetes Family Conflict Scale and the Diabetes Family Behavior Checklist, teamwork families reported significantly less conflict at 12 months. An analysis of HbA1c over the 12- to 24-month follow-up period indicated that more adolescents in the teamwork group (68%) than in the comparison group (47%) improved their HbA1c (P < 0.07). CONCLUSIONS: The data demonstrate that parent involvement in diabetes management tasks can be strengthened through a low-intensity intervention integrated into routine follow-up diabetes care. Moreover, despite increased engagement between teen and parent centered around diabetes tasks, the teamwork families showed decreased diabetes-related family conflict. Within the context of a broader cultural recognition of the protective function of parent involvement in the lives of adolescents, the findings of this study reinforce the potential value of a parent-adolescent partnership in managing chronic disease.

Adolescent↗

Prostaglandin, tumor necrosis factor alpha and neutrophils: causative relationship in indomethacin-induced stomach injuries.

Tumor necrosis factor alpha (TNF-alpha) has been suggested to play a critical role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal level and its relationship with prostaglandin E2 and neutrophils in indomethacin-induced gastric mucosal injury in rats. Indomethacin caused a time- and dose-dependent increase in gastric mucosal erosion, which was accompanied by a reduction in prostaglandin E2 followed by an increase in TNF-alpha level and neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury and the TNF-alpha increase. Depletion of neutrophils by methotrexate or reduction of TNF-alpha concentration by pentoxifylline markedly reduced indomethacin-induced mucosal damage. Pentoxifylline but not methotrexate prevented the increase in mucosal TNF-alpha level induced by indomethacin. It is suggested that depletion of prostaglandin E2 followed by an increase of TNF-alpha production and neutrophil infiltration in the gastric mucosa are important sequential processes in indomethacin-induced ulceration. Prevention of one of these processes would inhibit ulcer formation.

Animals↗

Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor that stimulates epithelial cell motility, invasion and morphogenesis. Its receptor is a transmembrane tyrosine kinase encoded by the Met proto-oncogene. Several studies have suggested a possible role for HGF/Met in tumor development and progression. To investigate the potential roles of Met in human lung cancer biology, we have studied the mRNA and protein expression of Met in normal lung tissue, primary non-small cell lung carcinoma (NSCLC), and NSCLC cell lines. The results indicated a differential pattern of Met expression among various subtypes of NSCLC. The majority of squamous cell carcinoma (SQCC), either in vivo or in vitro, expressed Met mRNA and its protein product at levels much lower than or similar to normal lung tissue or bronchial epithelium. Moreover, SQCC characteristically over-expressed a variant Met mRNA which corresponds to a 5' partially deleted transcript produced by alternative splicing. In contrast, the expression of Met mRNA and its protein product in adenocarcinoma (ADC) and large cell undifferentiated carcinoma were more heterogeneous. Overexpression was demonstrated in approximately 35% and 20% of these subtypes of NSCLC, respectively. Among ADC, intermediate to high levels of Met immunoreactivity correlated with greater degree of tumor differentiation. Furthermore, an accentuation of Met immunoreactivity was often noted in cancer cells at the advancing edge of tumors. These findings support a role for Met in lung cancer cell invasion and differentiation in vivo, but its expression and functions may be modified by the differentiation phenotype of the tumor cells.

Adenocarcinoma↗

Time saved with use of emergency warning lights and sirens during response to requests for emergency medical aid in an urban environment.

STUDY OBJECTIVE: To determine whether the use of warning lights and sirens saves a significant amount of time for ambulances responding to requests for medical aid in an urban, 2-tiered EMS setting. METHODS: A prospective design was used to determine run times for ambulances responding to calls with lights and sirens (Code 3), and for a similarly equipped "chase" vehicle traveling to the same call on the same route without lights and sirens (Code 2). Data were collected for run times, distance traveled, visibility, road surface condition, time of day, and day of the week. Simple statistics and analysis of variance were used to test for significant differences between Code 3 and Code 2 operation, as well as the other variables listed above. RESULTS: Sixty-four runs were timed during a 9-month period. The average Code 3 response interval was 4.46 minutes. The average Code 2 response interval was 7.48 minutes. The 3.02 minutes saved on average represents a significant time savings of 38.5% (P < .01). Run distance was the only variable that was statistically significant in affecting time saved during a Code 3 response. CONCLUSION: Code 3 operation by EMS personnel in an urban, 2-tiered EMS setting saved significant time over Code 2 operation when traveling to a call.

Ambulances↗

Nonsteroidal antiinflammatory drugs could reverse Helicobacter pylori-induced apoptosis and proliferation in gastric epithelial cells.

It remains controversial whether the harmful effects of Helicobacter pylori (Hp) and nonsteroidal antiinflammatory drugs (NSAIDs) are additive. We studied the effects of Hp (virulent and nonvirulent strains) and NSAIDs, alone or in combination, on apoptosis and proliferation of gastric epithelial cells in nonulcer dyspepsia (NUD) patients. Forty-four (25 Hp-positive and 19 Hp-negative) consecutive Chinese NUD patients with rheumatoid arthritis who had taken continuously NSAIDs for more than three months were recruited for this study. Another 41 (20 Hp-positive and 21 Hp-negative) NUD patients not on any NSAIDs were included as controls. All patients underwent a gastroscopy examination and gastric biopsies. Hp infection was confirmed by CLOtest, anti-Hp ELISA, and [13C]urea breath test. The CagA status was determined by the anti-CagA antibody assay. The degree of gastritis, apoptosis, and proliferation indices were determined with H&E staining, terminal uridine deoxynucleotidyl nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) immunostaining methods, respectively. A significantly higher apoptosis was observed in subjects who had Hp infection or had been consuming NSAIDs when compared with the controls. Unlike NSAID-treated subjects, patients with Hp infection were shown to have significantly enhanced cell proliferation. However, the increased apoptosis and proliferation in Hp-positive subjects were reversed by also taking NSAIDs. No correlation was found between apoptosis and proliferation in all the study groups. There was no association found between CagA expression or degree of gastritis with cell proliferation or apoptosis. It was demonstrated at the cellular level that NSAIDs could abrogate apoptosis or proliferation effects induced by Hp. Furthermore, the latter effects appeared not to be influenced by the virulent nature of the Hp strains.

Anti-Inflammatory Agents, Non-Steroidal↗

Up-regulation of lysozyme production in colonic adenomas and adenocarcinomas.

AIMS: The presence of lysozyme protein in some gastric adenomas and adenocarcinomas has been well documented. There have been relatively few studies investigating the presence of lysozyme in tumours of the large intestine and they show contrasting results. We aim to investigate the cellular source and expression of lysozyme in colonic adenomas and adenocarcinomas. METHODS AND RESULTS: We randomly selected 29 and 27 colonic adenomas and adenocarcinomas, respectively. Using in-situ hybridization (ISH) and immunohistochemistry (IHC), we found an up-regulation of lysozyme in the dysplastic epithelium of all the adenomas studied, with more than 80% of cases expressing moderate to strong signals. Although the up-regulation of lysozyme was also observed in adenocarcinomas, only 30% of the cases showed moderate to strong signals, mostly with an uneven distribution. Down-regulation of lysozyme in the severely dysplastic and invasive foci were noted in some cases of adenoma with malignant transformation. Normal colonic glands were consistently negative for lysozyme at both the mRNA and the protein level, but inflamed and immature regenerative colonic epithelium at the crypt base showed positive signals in a similar pattern to those observed in the dysplastic epithelium of the adenomas. CONCLUSIONS: Our results confirm that colonic epithelium can produce lysozyme and its expression is up-regulated in the dysplastic epithelium in adenomas and in invasive cancer cells. It is interesting that regenerative colonic epithelium showed a similar pattern of lysozyme expression as in adenomas. The loss of lysozyme secreting phenotype in most of the invasive tumours suggests that lysozyme may not confer an advantage to tumour progression.

Adenocarcinoma↗

Effects of fuel type, driving cycle, and emission status on in-use vehicle exhaust reactivity.

The introduction of reformulated gasolines significantly reduced exhaust hydrocarbon (HC) mass emissions, but few data are available concerning how these new fuels affect exhaust reactivity. Similarly, while it is well established that high-emitting vehicles contribute a significant portion of total mobile source HC mass emissions, it is also important to evaluate the exhaust reactivity from these vehicles. The objective of this study was to evaluate the relative influence on in-use vehicle exhaust reactivity of three critical factors: fuel, driving cycle, and vehicle emission status. Nineteen in-use vehicles were tested with seven randomly assigned fuel types and two driving cycles: the Federal Test Procedure (FTP) and the Unified Cycle (UC). Total exhaust reactivity was not statistically different between the FTP and UC cycles but was significantly affected by fuel type. On average, the exhaust reactivity for California Phase 2 fuel was the lowest (16% below the highest fuel type) among the seven fuels tested for cold start emissions. The average exhaust reactivity for high-emitting vehicles was significantly higher for hot stabilized (11%) and hot start (15%) emissions than for low-emitting vehicles. The exhaust reactivities for the FTP and UC cycles for light-end HCs and carbonyls were significantly different for the hot stabilized mode. There was a significant fuel effect on the mean specific reactivity (SR) for the mid-range HCs, but not for light-end HCs or carbonyls, while vehicle emission status affected the mean SR for all three HC compound classes.

Air Pollutants↗

Changing the process of diabetes care improves metabolic outcomes and reduces hospitalizations.

We designed and evaluated an ambulatory care intervention aimed at improving glycemic control and reducing hospitalizations in patients with insulin-dependent diabetes mellitus (IDDM). One hundred seventy-one youth with IDDM, ages 10-15, were assigned either to a Care Ambassador intervention (N = 89) or to standard care (N = 82). The intervention consisted of scheduling, confirming, and documenting medical follow-up for 24 months. During the study, the intervention group had more diabetes visits, 7.1 +/- 1.50 (mean +/- SD) Vs. 5.2 +/- 2.57 in the standard care group (P = 0.0001). In the at-risk subjects (baseline HbA1c 8.1%, N = 162), 50% of intervention subjects compared with 29% of standard care achieved HbA1c 8.6% while 17% of intervention subjects compared with 32% of standard care had values > 9.6% (P = 0.039). During follow-up, severe hypoglycemia and hospitalization/ER use occurred at half the rate in the intervention group compared with standard care. This specific, low-cost intervention aimed at increasing ambulatory medical visits in at-risk patients with diabetes improves metabolic outcomes and significantly reduces hospital/ER use.

Adolescent↗

Oncogenic activation of Neu/ErbB-2 in a transgenic mouse model for breast cancer.

Recent evidence has suggested that amplification and overexpression of erbB-2/neu is an important determinant in the initiation and progression of human breast cancer. Consistent with this assertion is the observation that transgenic mice that overexpress the neu proto-oncogene heritably develop mammary adenocarcinomas. More recently, we have demonstrated that activation of neu in many of these tumours occurs as a result of somatic mutations located within the transgene itself. Indeed, careful examination of the altered neu transcripts revealed the presence of in-frame deletions that encode aberrant Neu receptors lacking 5-12 amino acids within the extracellular domain, located adjacent to the transmembrane domain. Interestingly, the majority of the deletions analysed affect one of several conserved cysteine residues present within this region. Moreover, introduction of these activating mutations into the wild-type neu cDNA results in its oncogenic conversion. These observations suggest that this cysteine-rich region plays an important role in regulating the catalytic activity of Neu.

Amino Acid Sequence↗