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Biomedical subjects

L M Greene

Publications and source records attributed to L M Greene.

9 recordsLinked to original sources

Elevated expression and altered processing of fibulin-1 protein in human breast cancer.

The extracellular matrix protein fibulin-1 suppresses the motility and invasiveness of a variety of tumour cell types in vitro as well as the growth of fibrosarcoma tumours in nude mice. In this study, fibulin-1 protein expression in breast carcinoma specimens and normal breast tissue was evaluated immunohistologically. Fibulin-1 protein expression was also semiquantitatively assessed by immunoblot analysis in a collection of normal breast tissues (n=18), benign tumours (n=5) and breast carcinomas (n=39). In normal breast tissue, fibulin-1 protein expression predominated in the ductal epithelium and underlying myoepithelium, with weaker staining evident in the loose connective surrounding the ducts. Examination of breast carcinomas revealed that the tumour cells also expressed fibulin-1 protein. The level of mature fibulin-1 polypeptide (100 kDa) was higher in the breast carcinoma specimens as compared to normal breast tissue (Mann-Whitney U-test, P=0.0005). In addition to the mature fibulin-1 polypeptide, several smaller sized polypeptides of 55, 50 and 25 kDa were detected using monoclonal antibodies reactive towards an epitope located at the N-terminus of fibulin-1. The immunoreactive 50 kDa polypeptide was detected more frequently in breast carcinoma specimens than in normal breast tissue (chi(2)=17.22, P<0.0001). Furthermore, the ratio of the 50 kDa fragment to the mature fibulin-1 polypeptide correlated with the level of oestrogen receptor alpha (Spearman correlation coefficient, rs=0.49, P<0.003, n=36) and progesterone receptor (rs=0.43, P=0.008, n=36) expression in the tumour specimens. Taken together, these findings indicate that elevated expression and altered processing of fibulin-1 is associated with human breast cancer.

Antibodies, Monoclonal↗

Human fibulin-4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues.

Here, we report the identification of a human orthologue of fibulin-4, along with analysis of its biosynthetic processing and mRNA expression levels in normal and tumour tissues. Comparative sequence analysis of fibulin-4 cDNAs revealed apparent polymorphisms in the signal sequence that could account for previously reported inefficient secretion in fibulin-4 transfectants. In vitro translation of fibulin-4 mRNA revealed the presence of full-length and truncated polypeptides, the latter apparently generated from an alternative translation initiation site. Since this polypeptide failed to incorporate into endoplasmic reticulum membrane preparations, it was concluded that it lacked a signal sequence and thus could represent an intracellular form of fibulin-4. Using fluorescence in situ hybridisation analysis, the human fibulin-4 gene was localised to chromosome 11q13, this region being syntenic to portions of mouse chromosomes 7 and 19. Considering the fact that translocations, amplifications and other rearrangements of the 11q13 region are associated with a variety of human cancers, the expression of human fibulin-4 was evaluated in a series of colon tumours. Reverse transcription-polymerase chain reaction analysis of RNA from paired human colon tumour and adjacent normal tissue biopsies showed that a significant proportion of tumours had approximately 2-7-fold increases in the level of fibulin-4 mRNA expression. Taken together, results reported here suggest that an intracellular form of fibulin-4 protein may exist and that dysregulated expression of the fibulin-4 gene is associated with human colon tumourigenesis.

Amino Acid Sequence↗

The role of radiology in pulmonary infectious disease.

This review of recently published papers focuses on the recent tious disease. Despite advances in thoracic imaging, the chest roentgenogram combined with the clinical history remain the cornerstone in the diagnosis, staging, and follow-up of pulmonary infectious disease. Examination of all prior films to document preexistent anatomic pulmonary or cardiac disease and to establish the progression or regression of the pulmonary infiltrate is essential prior to proceeding with more costly imaging.

Diagnosis, Differential↗

New peripherally inserted midline catheter: a better alternative for intravenous antibiotic therapy in patients with cystic fibrosis.

A study was performed on outpatients with cystic fibrosis (CF) to evaluate the performance of an over-the-needle peripherally inserted midline catheter for the delivery of 2-week courses of antibiotic therapy. The midline is a 7-inch catheter inserted in the antecubital region with the tip located in the axillary region. It is made of a newly developed biomaterial that softens and expands upon contact with body fluids. The hypotheses for the study were that the midline catheter: 1) is useful for intermediate-length therapies; 2) can prevent multiple 3-day conventional peripheral catheter restarts; 3) can prevent or delay the use of more invasive central devices; 4) is comfortable for patients; and 5) is economical. A total of 41 midlines were inserted in 27 patients with an average age and weight of 22 years and 109 pounds, respectively. Prior to this study implanted ports and primarily conventional short peripheral catheters were used to administer I.V. therapy to these patients; fifty percent of these short peripheral catheters failed within 2.6 days. At 2 weeks of dwell, 80% of the midline catheters placed in these patients were still indwelling. Also, 80% of all midline catheter removals were for non-catheter-related reasons. There were no cases of midline catheter phlebitis. In contrast, the phlebitis rates published for peripherally inserted central catheters (PICCs) and conventional short peripheral catheters at 7 days of dwell are 20% and greater than 51% respectively. The midline catheters were comfortable and well liked by most patients and became more economical than conventional peripheral catheters for therapies lasting approximately 6 days through 1 to 2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nutritional support in patients with inflammatory bowel disease.

Total parenteral nutrition with bowel rest has been used as primary therapy to reduce disease activity and achieve remission in patients with inflammatory bowel disease (IBD). However, results are short-lived and similar success can be attained through total enteral nutrition with highly specialized elemental or semielemental formulas. Enteral nutrition costs less than parenteral nutrition, maintains gut integrity, stimulates immunocompetence, and helps to control symptoms and overall disease activity. Increased use of enteral formulas can be expected in the future. The role of diet in management of IBD is currently under scrutiny. No one diet is appropriate for all patients, but restriction of fat, fiber, lactose, or oxalate may be necessary to help alleviate symptoms and minimize the risk of complications.

Enteral Nutrition↗

Use of residual volume as a marker for enteral feeding intolerance: prospective blinded comparison with physical examination and radiographic findings.

High gastric residual volumes (RVs) are a frequent cause for cessation of total enteral nutrition (TEN). This study was designed to determine the RV that indicates intolerance or inadequate gastric emptying and to compare the RV findings in a blinded fashion with those findings obtained on physical examination and radiography. Twenty healthy normal volunteers (HNV), 8 stable patients with gastrostomy tubes (GTP), and 10 critically ill patients (CIP) were evaluated prospectively for 8 hours while receiving TEN. No subjects were clearly intolerant (ie, vomiting, aspiration). Of the total RVs recorded, 13.1% were greater than or equal to 150 mL in the CIP group, whereas only 2.4% of the RVs were greater than or equal to 150 mL in the HNV group. None of the RVs in the GTP group were greater than or equal to 150 mL. Objective scores on physical examination failed to correlate with RV (p = .397), as did objective scores on radiography (p = .742). However, objective scores on physical examination were significantly related to scores on radiography (p = .016). Abnormal physical examination findings were found in 4 out of 11 patients (GTP + CIP) with RVs less than 100 mL and in 6 out of 7 with RVs greater than or equal to 100 mL. Abnormal radiographic results were found in 6 out of 11 patients with RVs less than 100 mL, in 7 out of 7 patients with RVs greater than or equal to 100 mL, and in 4 out of 20 HNVs. There was no difference in RVs obtained from the supine or right lateral decubitus positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis.

BACKGROUND: This prospective study was designed to compare the safety, efficacy, cost, and impact on patient outcome of early total enteral nutrition (TEN) vs total parenteral nutrition (TPN) in acute pancreatitis. METHODS: Patients admitted with acute pancreatitis or an acute flare of chronic pancreatitis, characterized by abdominal pain and elevated serum amylase and lipase, were randomized to receive either isocaloric and isonitrogenous TEN (via a nasojejunal feeding tube placed endoscopically) or TPN (via a central or peripheral line) started within 48 hours of admission. RESULTS: Thirty patients were studied over 32 admissions (TEN given on 16 and TPN on 16) for acute pancreatitis. There were no differences on admission in mean age, Ranson criteria, multiple organ failure score (MOF), or APACHE III score between TEN and TPN groups. Although slower to approach goal feeding over the first 72 hours of admission, TEN patients received 71.3% goal calories by day 4 vs 85.2% for TPN patients (not significant). There were no deaths and no differences between groups in serial pain scores, days to normalization of amylase, days to diet by mouth, serum albumin levels, or percent nosocomial infection. However, the mean cost of TPN per patient was over four times greater than that for TEN ($3294 vs $761, respectively, p < .001). Mean serial Ranson criteria, APACHE III, and MOF scores recorded every 2 to 3 days decreased in the TEN group, whereas those in the TPN group increased. Only the difference in the third Ranson criteria (mean 6.3 days after admission) for the TEN and TPN groups (0.5 vs 2.8, respectively) reached statistical significance (p = .002). Stress-induced hyperglycemia was worse in the TPN group, as serum glucose levels increased significantly over the first 5 days of hospitalization (p < .02), whereas those in the TEN group showed no significant change. An exacerbation of pancreatitis, occurring in one TEN patient when the nasojejunal tube was dislodged into the stomach, resolved after placement back in the jejunum. Three patients who became asymptomatic and normalized amylase on TEN flared upon advancing to diet by mouth. CONCLUSIONS: TEN for acute pancreatitis is as safe and effective, but is significantly less costly than TPN. Compared with TPN, TEN may promote more rapid resolution of the toxicity and stress response to pancreatitis. TEN via jejunal feeding should be used preferentially in this disease setting.

APACHE↗