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Biomedical subjects
Publications and source records attributed to J Lennon.
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The morphology and behaviour of the chromosomes of dinoflagellates during the cell cycle appear to be unique among eukaryotes. We used synchronized and aphidicolin-blocked cultures of the dinoflagellate Crypthecodinium cohnii to describe the successive morphological changes that chromosomes undergo during the cell cycle. The chromosomes in early G(1) phase appeared to be loosely condensed with numerous structures protruding toward the nucleoplasm. They condensed in late G(1), before unwinding in S phase. The chromosomes in cells in G(2) phase were tightly condensed and had a double number of arches, as visualised by electron microscopy. During prophase, chromosomes elongated and split longitudinally, into characteristic V or Y shapes. We also used confocal microscopy to show a metaphase-like alignment of the chromosomes, which has never been described in dinoflagellates. The metaphase-like nucleus appeared flattened and enlarged, and continued to do so into anaphase. Chromosome segregation occurred via binding to the nuclear envelope surrounding the cytoplasmic channels and microtubule bundles. Our findings are summarized in a model of chromosome behaviour during the cell cycle.
BACKGROUND: The purpose of this study was to determine the effects of periodontal treatment with a sustained-release, biodegradable gel containing 8.5% doxycycline on the anaerobic flora and on antibiotic susceptibility patterns associated with subgingival plaque and saliva. METHODS: Forty-five subjects with adult periodontitis were entered into a parallel design, single-blind study of 6 months' duration. The subjects were randomized to receive either doxycycline treatment (n = 23) or oral hygiene instruction/reinforcement (n = 22). Saliva and subgingival plaque samples were collected prior to and at 7, 21, 91, and 182 days after initiation of treatment. The proportion of the cultivable flora resistant to 10 microg doxycycline/ml was determined relative to total anaerobic counts, and the 3 most predominant colony types resistant to doxycycline were individually enumerated. A representative of each was subcultured, identified to genus and species level, and tested for its susceptibilities to 6 antibiotics. RESULTS: A significant decrease (P <0.01) in total anaerobic counts following doxycycline treatment caused a transient increase in the proportion, but not in the actual counts, of doxycycline-resistant bacteria recovered from both plaque and saliva at 7 and 21 days but not at 91 or 182 days. The same doxycycline-resistant taxa were recovered at all sample periods including baseline. Regardless of treatment, the isolates were similarly distributed and belonged to the same bacterial groups. CONCLUSIONS: Doxycycline treatment significantly reduced the anaerobic population in plaque but did not result in a change in either the number of resistant bacteria present or the acquisition of antibiotic resistance.
BACKGROUND: The purpose of this study was to determine whether treatment with subantimicrobial dose doxycycline (SDD), 20 mg bid, exerted an antimicrobial effect on the microflora associated with adult periodontitis. METHODS: Following the approval of the protocol and informed consent forms by the respective IRBs at the University of Florida and West Virginia University, 76 subjects with adult periodontitis were entered and randomly assigned to receive SDD or placebo. A split-mouth design was utilized, with each subject receiving subgingival scaling and root planing (SRP) in two quadrants immediately following baseline data collection, while the remaining two quadrants were left unscaled (non-SRP). Microbial samples were collected prior to treatment, after 3, 6, and 9 months of treatment, and after 3 months of no treatment. The samples were examined by microscopy and by enumeration on selective and non-selective media. RESULTS: All treatments resulted in statistically significant decreases in the proportions of spirochetes and motile rods (P <0.05) and in an increase in the proportion of coccoid forms (P <0.0001) relative to baseline. No between-treatment differences were detected between the SDD and placebo treatments in either the SRP or non-SRP design, with the exception of the small and large spirochetal groups. The spirochetal proportions present in the SDD group were significantly lower (P<0.05) than the paired placebo group during the 9-month treatment and was preceded by a significant decrease (P<0.01) in the proportion of microbiologic sample sites that bled on probing. No between- treatment differences were detected in any of the other microbial parameters. CONCLUSION: The microbial differences observed were attributed to the anticollagenase and anti-inflammatory properties of SDD and not to an antimicrobial effect.
Wild type, partially and fully-deglycosylated human sex steroid-binding protein (SBP or SHBG) cDNAs lacking the native cucaryotic signal sequence were cloned into a yeast expression vector containing the Saccharomyces cerevisiae alpha-factor for extracellular secretion. Following transformation into Pichia pastoris, the wild type and all constructed mutants were successfully expressed. The levels were lower for the deglycosylated mutants indicating that oligosaccharide side chains may play a role in SBP secretion. Under fermentation conditions, the wild type protein was expressed at a level of 4 mg/l while the fully-deglycosylated mutant T7A/N351Q/N367Q was expressed at about 1.5 mg/l. The latter was purified from several fermentation runs and was found to be completely deglycosylated, electrophoretically homogeneous and fully active. The aminoterminus was found to have the sequence NH2QSAHDPPAV- indicating that cleavage of the alpha-factor occurred at the A(+7)-Q(+8) peptide bond. The molecular mass of the subunit was determined to be 39,717.8 Da, which is in complete agreement with the amino acid sequence of the T7A/N351Q/N367/Q mutant. The equilibrium constants for the dissociation of 5alpha-dihydrotestosterone and steroid binding specificity were found to be identical to that of the human plasma protein indicating that the missing N-terminal segment NH2-LRPVLPT and the removal of oligosaccharide side chains do not affect the stability and active conformation of the protein. In conclusion, the data presented reveal that the SBP mutant T7A/N351Q/N367/Q is the protein of choice for solving the three-dimensional structure.
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Removal of bile duct stones during endoscopic retrograde cholangiopancreatography (ERCP) usually includes papillotomy. Papillotomy is associated with occasional complications and in addition, the longterm sequelae of papillotomy in young patients having laparoscopic cholecystectomy remain unclear. As an alternative to papillotomy, this study prospectively evaluated the efficacy and safety of endoscopic balloon sphincteroplasty to facilitate bile duct clearance. Of 32 patients with bile duct stones (diameter 3-30 mm) at ERCP, sphincteroplasty was considered inappropriate in four patients because of stone size (> 20 mm) necessitating papillotomy for bile duct clearance. Sphincteroplasty was performed in the remaining 28 patients to permit duct clearance by dormier basket, balloon or mechanical lithotripsy. The bile duct was cleared in 22 patients (79%) while additional measures including papillotomy or stent insertion were required in the remaining six patients (21%) because of stone size or technical difficulties. There was no associated papillary haemorrhage. Pancreatitis was seen in one patient (4%) but resolved within 24 hours. Our preliminary experience suggests that sphincteroplasty is a safe and effective sphincter preservation technique that significantly reduces the necessity for papillotomy in the management of bile duct stones.
Benign papillary stenosis is an uncommon but well recognised cause of recurrent biliary pain usually in post-cholecystectomy patients characterised by biliary dilatation without bile duct calculi or malignancy. Endoscopic or surgical papillotomy is the recommended treatment but may be associated with a higher complication rate than when performed for bile duct stones. We report 2 cases of papillary stenosis treated by endoscopic balloon dilatation or "sphincteroplasty", as a less traumatic intervention which improved biliary drainage and provided symptomatic relief. Our preliminary experience suggests more widespread evaluation of balloon sphincteroplasty should be considered for papillary stenosis.
In order to study the effect of clofazimine, a powerful antimycobacterial and antiinflammatory agent, 49 patients with active Crohn's disease were randomized to either corticosteroids plus clofazimine 100 mg daily (N = 25) or to steroids and matching placebo (N = 24). A total of 28 patients (58%) went into disease remission (clofazimine 16, placebo 12; P = NS) with a fall in disease activity score from 10.5 +/- 4.4 to 3.3 +/- 3.5. Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study (clofazimine 12, placebo 6; P = NS). Side effects were minor and consisted of skin rash and increased pigmentation. Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn's disease but may have a role in either disease maintenance or combination chemotherapy.
In the first year from October 1990 since starting the procedure 65 laparoscopic cholecystectomies were carried out on one surgical service. There were 4 planned open cholecystectomies and 8 laparoscopic procedures converted during the same period: 7 of these were in the first 3 months with only 1 of the last 53 being opened. Surgery was carried out during the same admission in 22 patients presenting as emergencies: acute cholecystitis (9), colic (6), pancreatitis (3), jaundice (4). Two patients had later laparotomies for complications; one patient bled from the umbilical stab and with ongoing peritonism had a pelvic haematoma drained on day 5 and a second was opened following a bile leak caused by a displaced cystic duct clip--both recovered uneventfully. Peroperative cholangiography was performed in 13 patients; 2 were positive (15%) and had ERCP papillotomy 3 days post op without complication. One patient who presented with pancreatitis had ERCP performed post-op without incident. Seven patients had laparoscopic cholecystectomy following papillotomy for common duct stones. The gallbladder was extracted per umbilicus in 45 (3 wound infections) and per right subcostal stab in 20 (no infections). Mean hospital stay was 48 hours (1-4 days) in uncomplicated cases. In conclusion, the learning curve is associated with higher conversion rates. Extraction through pliable hypochondrial muscles is easier and may be safer and less traumatic. Perioperative endoscopic papillotomy is safe and effective for choledochal stones.
Antibody directed to the O-specific polysaccharide (Ps) side chain of Pseudomonas aeruginosa LPS provides immunotype-specific protection against infection by virtue of enhancing opsonophagocytosis. We have developed a syngeneic anti-idiotypic antibody (mAb2) directed to a functionally active monoclonal immunotype 1 Ps-antibody (mAb1). The mAb2 performed as a molecular mimic of Ps as evidenced by 1) blocking of mAb1/mAb2 interaction by Ps, 2) blocking of mAb1/Ps binding by mAb2, 3) cross-species binding of mAb2 to human Ps antibodies from individuals immunized with the same immunotype 1 Ps, and 4) induction of anti-LPS antibody by immunization with mAb2 in syngeneic mice. Our studies thus show that an anti-idiotypic antibody may functionally mimic the O-polysaccharide of P. aeruginosa LPS, and bind to cross-reactive Id present in human Ps antibodies. We have further shown that this anti-idiotypic antibody induces anti-LPS antibody when used as an Ag in syngeneic mice, suggesting that this approach may eventually be used to successfully immunize humans.
A situationally specific measure of trait anxiety based on the Endler model was a better predictor of pre-operative state anxiety than the STAI trait anxiety scale in 54 patients undergoing colonoscopy. Lower self-reported pre-operative anxiety was found for (a) repressors, who report low trait anxiety and high defensiveness on the Marlowe-Crown scale, than for (b) truly low anxious patients, who report low trait anxiety and low defensiveness.
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We describe a patient with disseminated sarcoidosis, who had granulomatous enterocolitis with radiological narrowing of the terminal ileum, and was presumed to have Crohn's disease. At autopsy, there were numerous sarcoid-like granulomata throughout the mucosa of the large and small bowel, but no transmural inflammation, lymphoid aggregates, or strictures, thus making Crohn's disease unlikely. It is proposed that a granulomatous enterocolitis resembling Crohn's disease can be a manifestation of disseminated sarcoidosis.
Although common in Japan, early gastric cancer is rarely seen in Western countries and generally accounts for only 7 to 10 percent of all gastric malignancies. Eleven patients with early gastric cancer seen over a 10 year period have been reviewed for clinical and pathologic features, method of diagnosis, treatment, and prognosis. The symptoms usually consisted of vague epigastric pain or dyspepsia, but anorexia, weight loss, anemia, and hypoalbuminemia were not commonly seen. Barium meal examination was not helpful in the diagnosis in 50 percent of the patients. The diagnosis was made by endoscopic biopsy of abnormal areas of the stomach, although in 6 of 11 patients, there was no macroscopic suspicion of malignancy. All patients were treated by surgical resection. The tumor was confined to the mucosa in five patients and had infiltrated the submucosa in six patients. The lymph nodes were free of tumor in every patient. At last follow-up, seven patients had survived more than 5 years after operation and were well, although recurrent tumors developed in two patients 3 and 4 years postoperatively but were detected early by endoscopic surveillance. Early gastric cancer has a good prognosis after surgical resection, but the symptoms are vague and the diagnostic tests can be misleading. A vigorous approach to investigation, treatment, and follow-up is necessary to achieve satisfactory results.
Esophageal function in 20 subjects with diabetes mellitus was assessed using esophageal manometry, 24-hr ambulatory esophageal pH monitoring, and esophageal scintigraphy. Seven patients had abnormal esophageal manometric studies, and this abnormality was significantly associated with peripheral neuropathy. Almost half of the subjects studied demonstrated excessive gastroesophageal acid reflux, but there was no correlation between the likelihood of abnormal reflux and the presence of peripheral neuropathy. Esophageal scintigraphy was relatively insensitive in the detection of abnormal esophageal function in diabetics.