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Biomedical subjects

K H Nguyen

Publications and source records attributed to K H Nguyen.

28 records · Page 2Linked to original sources
PubMed1996

Alterations in the secretory response of non-obese diabetic (NOD) mice to muscarinic receptor stimulation.

Salivary gland secretion in non-obese diabetic (NOD) and BALB/c mice was evaluated following stimulation with the muscarinic receptor agonist pilocarpine. Both saliva flow rates and total protein were similar in BALB/c and prediabetic NOD mice. With diabetes onset in NOD mice, the saliva flow rate and protein concentration were dramatically reduced. The level of cyclic AMP (cAMP) generated 10 min following agonist injection was similar for the parotid gland of BALB/c and prediabetic and diabetic NOD mice but was reduced in diabetic NOD mice. In the submandibular gland both prediabetic and diabetic NOD mice showed a reduced potential for the generation of cAMP compared with BALB/c mice. The parotid gland from NOD mice had elevated levels of basal and muscarinic receptor agonist (carbachol)-stimulated concentrations of inositol phosphate intermediates in in vitro assays compared with BALB/c animals, while in the submandibular gland of NOD mice, basal and agonist-stimulated concentrations of inositol phosphate intermediates were reduced relative to BALB/c. An evaluation of muscarinic receptor density showed a reduction with diabetes onset for the parotid gland, while a similar level was observed in prediabetic NOD and BALB/c mice. The receptor density was decreased for both the prediabetic and diabetic NOD submandibular glands compared with BALB/c animals. Sera from diabetic NOD but not BALB/c mice immunoprecipitated radiolabeled muscarinic receptor, indicating the presence of autoantibody to the receptor in diabetic mice. Thus, the reduction of muscarinic agonist response in NOD mice may be due, in part, to a generalized reduction in signal transduction components most evident in the prediabetic and diabetic submandibular gland and to a less certain degree in the parotid gland from diabetic NOD mice as a consequence of autoantibodies directed against cell surface antigens.

Animals↗
PubMed1996

Cell cycle control in isoproterenol-induced murine salivary acinar cell proliferation.

The eukaryotic cell cycle is a summary of a complex network of signal transduction pathways resulting in both DNA replication and cell division. Cyclin-dependent kinases (CDKs) control the cell cycle in all eukaryotes, whereas other proteins, known as cyclins, act as their regulatory subunits. Chronic injection with isoproterenol (ISO) can induce acinar cell proliferation in rodent salivary glands. Cyclins and CDK proteins from control and ISO-treated murine parotid acinar cells were detected by using Western blotting techniques. By comparing the expression of these cell cycle regulatory kinases in the parotid acinar cell transition from a quiescent state to a hypertrophic state, we found rapid increases in the protein levels of all CDKs, cyclin D and proliferating cell nuclear antigen (PCNA). The highest protein levels for CDKs and cyclins appeared at about 72 hr of ISO stimulation and were coincident with the highest rate of increase in gland wet weight. After 72 hr, the increase of both cell cycle protein and gland wet weight began to subside. By using a co-immunoprecipitation method, the following cell cycle regulators (CDK-cyclin complexes) were detected, CDK4-cyclin D, CDK2-cyclin E, CDK2-cyclin A, and cdc2-cyclin B, along with an increase in kinase activity over control untreated animals. Additionally, we detected significant decreases in the newly isolated CDK inhibitor (CKI) p27kip but not Wee 1 kinase. The increased levels of CKI correlated with a decrease in kinase activity of CDK/cyclin complexes by 144 hr of chronic isoproterenol treatment. Our data suggest that the holoenzymes for cell cycle control (cyclin-CDK complexes) function as a final regulatory mechanism leading to salivary gland acinar cell proliferation. The gradual decline in protein levels of the CDKs and cyclins after 3 days of chronic treatment further indicates that ISO-induced proliferation of parotid acinar cells is self-limiting and non-tumorigenic.

Animals↗
PubMed1993

Absorption of insulin in the peritoneal cavity in a diabetic animal model.

This study was conducted to determine if different anatomical sites within the peritoneal cavity have different capacities for portal insulin absorption. Diabetic male Sprague-Dawley rats were studied. They were anesthetized and injected with streptozotocin. Blood glucose was measured before and after insulin (1 U/kg) was applied directly to the omentum, serosal surface of cecum, or parietal peritoneum or injected subcutaneously. In a control group, blood glucose was measured at intervals without administering insulin. In addition, insulin labeled with radioactive iodine (125I) was applied to the same three locations in the peritoneal cavity or injected intravenously. Animals were sacrificed at 1, 5, 15, or 30 mins, and radioactivity was measured in excised livers and in blood samples. Blood glucose in the omental group responded to insulin with a greater hypoglycemic effect than in the peritoneal and control groups. The percentage of radioactivity recovered in liver was significantly higher in the omental than in the serosal and peritoneal groups at 1 and 5 mins. The ratio of liver-to-blood radioactivity was also significantly higher in omental than in serosal and peritoneal groups and higher in the serosal than in the peritoneal group at 5 mins. The data suggest that, in this model, the omentum is a better site for insulin absorption than serosa or parietal peritoneum and that significant portal venous absorption of insulin occurs.

Animals↗
PubMedDate not supplied

Juxtaposition of the atrial appendages: a clinical series of 22 patients.

Because the outcome of a large clinical series of patients with juxtaposition of the atrial appendages (JAA) has not previously been reported, a retrospective study was performed on patients diagnosed with JAA at a tertiary medical center. Patients with JAA were identified through a computerized database search, and echocardiograms and medical records of patients with JAA were reviewed. Twenty-two patients with JAA were identified, with an overall incidence of 0.28%. All but 2 patients were diagnosed prospectively with JAA by echocardiography. The lesion-specific incidences and associated lesions were similar to those of large autopsy and surgical series. Abnormal conotruncal anatomy was more frequently seen with juxtaposition of the right atrial appendage (JRAA) vs juxtaposition of the left atrial appendage (JLAA) (14/15 vs 4/7), as was atrial outlet obstruction (6/15 vs 2/7). JLAA was more frequently associated with complex atrioventricular anatomy (3/7 vs 1/15). Patients with JAA underwent single ventricle palliation in 11/22 cases with 6 deaths; biventricular repair was performed in 8/22 cases with no deaths. Surgical outcomes for patients with JRAA and JLAA were similar, and survival was predominantly influenced by suitability for biventricular repair.

Adolescent↗
PubMedDate not supplied

The Bentall procedure in patients with Marfan's syndrome.

From 1985 to 1996, 18 patients with Marfan's syndrome underwent the Bentall procedure at Mount Sinai Hospital. They are compared with 38 patients aged < 40 without Marfan's syndrome who also underwent composite valve-graft replacement of the ascending aorta. The mean age of the non-Marfan group was 33 while that of the Marfan group was 29. Nearly three-quarters of each group were male. Aortic dissection was present in 33% of the Marfan group but only in 18% of the other group. Seventy-eight percent of the Marfan patients and 89% of the non-Marfan patients had aortic regurgitation. Twenty-one percent of the patients in the control group nevertheless had gross aortic pathology suggestive of Marfan's syndrome and may have had variants of the syndrome; 26% of the non-Marfan group had a bicuspid aortic valve. A modification of the Bentall procedure with implantation of coronary artery buttons was performed in the majority of the patients in both groups. Three patients, all in the group with Marfan's syndrome, required a concomitant mitral valve procedure. There was one death in each group. Two non-Marfan patients required reoperation; neither had dissection. Four patients with Marfan's syndrome underwent reoperation for distal disease in the aorta; they comprised one third of the Marfan patients who had aortic dissection. Three late complications occurred in the group with Marfan's syndrome: progressive cardiomyopathy; myocardial infarction; and late tamponade. There were also two late sudden deaths in the group with Marfan's syndrome, which may have been the consequence of aortic rupture. No difference in immediate operative mortality following the Bentall procedure was noted between patients with and without Marfan's syndrome, but young patients without Marfan's syndrome seem to have better event-free and long-term survival. In patients with Marfan's syndrome, the presence of acute dissection makes reoperation more likely, and sudden death from rupture still occurs despite careful postoperative surveillance. A higher incidence of severe mitral valve disease was found among young patients with Marfan syndrome than in controls.

Adolescent↗
PubMedDate not supplied

Identification of risk factors in patients undergoing thoracoabdominal aneurysm repair.

Developments and advances in surgical and anesthetic techniques have lead to increased survival in patients undergoing complex thoracic aortic aneurysm repairs. The decision to operate, however, continues to be based in a large degree on the clinical impression of the patient's ability to withstand the rigors of the procedure. As part of the ongoing effort of our department to further elucidate those parameters that impart added risk to patients, the diameters and volumes of CT-imaged aortas were determined for 67 surgical and nonoperatively managed patients. Significant differences were found between those patients not requiring surgery, and both those undergoing operation and those that died of rupture. Similarly, the average yearly increase in volume in surgical and rupture patients was higher than that of nonoperatively managed patients. Those patients who smoked also were found to have a significant yearly increase in size of their aortas relative to those patents that did not. An algorithm for managing patients presenting with thoracoabdominal aneurysms based upon size at initial presentation, change in annual diameter and volume, and estimated risk for paraplegia is presented.

Adult↗
PubMedDate not supplied

Use of hypothermic circulatory arrest for cerebral protection during aortic surgery.

Optimal use of hypothermic circulatory arrest during aortic surgery requires understanding of its physiology. Research in laboratory animals and clinical observations have now documented that considerable residual cerebral metabolism remains with cooling to levels of 15-18 degrees C, especially if cooling intervals are short, reflected by persistent jugular venous desaturation. Cooling should be continued to below 15 degrees C if the duration of HCA is expected to exceed 20 minutes, and continued until jugular venous saturations exceed 95%. There is considerable laboratory evidence that even short durations of HCA are followed by a prolonged interval of increased cerebral vascular resistance during which cerebral metabolism is maintained at normal levels by markedly increased oxygen extraction. Clinical observations have now confirmed that considerable jugular venous desaturation is present in patients following HCA: it is more pronounced with prolonged HCA, and is still present as late as six hours after the start of rewarming. This reinforces the concept of a prolonged postoperative vulnerable interval following HCA, during which any compromise in oxygen delivery has the potential for producing cerebral injury. Several adjunctive measures have been shown to improve outcome following HCA. The simplest and most important is topical hypothermia: packing the head in ice during the interval of HCA. Retrograde cerebral perfusion (RCP) has also been shown to improve EEG recovery as well as histological and behavioral outcome in laboratory animals following prolonged HCA, but some of its effect may be secondary to its efficacy in keeping the brain cold, since RCP provides very low rates of flow and supports metabolism at a much lower level than antegrade perfusion at the same temperature. But despite the clear superiority of antegrade perfusion, and the documentation of some benefits of RCP in laboratory measures of cerebral protection, clinical results using RCP and ACP have not yet demonstrated the superiority of these methods over use of HCA alone, perhaps because these modalities are usually employed in patients with unusually high risk of neurological injury: those with dissection or with clot or atheroma in the aorta. Nevertheless, recent years have seen considerable reduction in mortality following aortic surgery, especially in older patients, and a trend toward a lower incidence of permanent neurologic dysfunction. The presence of preoperative rupture or hemodynamic compromise, and of clot or atheroma in the aorta, remain the most significant risk factors both for death and occurrence of stroke.

Animals↗
PubMedDate not supplied

Assessment of bromhexine as a treatment regimen in Sjögren's syndrome-like disease in the NOD (non-obese diabetic) mouse.

OBJECTIVE: Bromhexine has been reported to alleviate the xerostomia and xerophthalmia associated with secondary Sjögren's syndrome. The aim of this study was to determine if it might prove useful in the treatment of Sjögren's syndrome-like disease of the NOD mouse model for autoimmune sialoadenitis. METHODS: Groups of mice were divided into sets receiving 60 mg/kg bromhexine in drinking water and control pair-fed animals. The efficacy of drug treatment was assessed by weekly measurement of stimulated saliva volumes, protein concentration, and amylase activity. At termination (20 weeks) submandibular and lacrimal glands were removed to assess the levels of lymphocytic infiltration by histological evaluation under light microscopy. RESULTS: Control and bromhexine-treated groups of mice showed no difference in the loss or rate of reduction in stimulated saliva flow over the 12 weeks of treatment. No differences were noted in the protein concentration and amylase loss with increasing age of the animals. Similar temporal changes in total protein profiles and aberrant expression of the 20 kDa parotid secretory protein isoform were observed by SDS-polyacrylamide gel profiles and Western bolt analysis. Histological evaluation of exocrine gland sections failed to detect any reduction in focal lymphocyte infiltration. CONCLUSION: Bromhexine therapy did not alter the development or severity of Sjögren's syndrome-like disease in the NOD mouse model for autoimmune sialoadenitis.

Amylases↗