Biomedical subjects

D E Anderson

Publications and source records attributed to D E Anderson.

At least 127 records · Page 7Linked to original sources

PubMed1993

Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals.

Free radicals react with nitrones to form stable nitroxides which can be identified by ESR spectroscopy. Unfortunately, little is known regarding the pharmacological properties of these compounds. In this study, three commonly used nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO), alpha-phenyl-tert-butylnitrone (PBN), and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), were found to induce relaxation of preconstricted isolated rat pulmonary artery rings. Additional experiments with PBN indicated that vasorelaxation could not be attributed to production of endothelial derived factors, prostaglandins, or free radicals. Patch-clamp techniques revealed reversible calcium channel blockade with PBN at a concentration below that needed to detect free radicals. Calcium channel blockade probably accounts for the vasorelaxation observed in the isolated ring preparations described here, and should be considered when using nitrone spin-traps both in in vivo and clinical studies.

Animals↗

PubMed1993

Enhancement of antigen-induced bronchoconstriction after intravascular complement activation with cobra venom factor. Reversal by granulocyte depletion.

Our previous studies have demonstrated that activation of the C system with cobra venom factor (CVF) in a passively sensitized guinea pig results in an enhanced bronchoconstrictor response to Ag but not to other constrictor agents. Thus, our immediate goal was to determine the mechanism of the CVF-induced enhancement of the Ag-induced bronchoconstriction. Isolated airways from sensitized guinea pigs that had been treated with CVF responded normally to Ag. Because such a system lacks the normal circulating cell populations, we hypothesized that the CVF-induced enhancement of the Ag-induced bronchoconstriction was dependent on the presence of circulating white blood cells or platelets. Guinea pigs were depleted of circulating granulocytes, platelets, or both using specific antisera and the effect on the CVF-induced enhancement of the Ag-induced bronchoconstriction was determined. We found that CVF treatment did not result in an enhanced Ag-induced bronchoconstriction in guinea pigs depleted of either granulocytes or both granulocytes and platelets. However, the enhanced response was still apparent in guinea pigs depleted of just platelets. We investigated the effects of CVF itself and found that CVF treatment did not alter the number, or percentages, of different cell populations in the bronchoalveolar lavage, did not alter the protein or albumin content of the lavage fluid or the wet:dry ratio of the lung. In addition, CVF did not cause an increase in airway microvascular permeability as assessed by leakage of Evans blue. However, CVF did substantially increase granulocytes sequestered in the lung as measured by increased myeloperoxidase content. Thus, C activation by CVF results in an increase in neutrophils in the lung and an enhanced Ag-induced bronchoconstriction dependent on the presence of circulating granulocytes. These studies suggest that C activation and/or retention of granulocytes in the lung may be important in determining the severity of an Ag-induced bronchoconstriction.

Animals↗

PubMed1993

Hydrophobic core repacking and aromatic-aromatic interaction in the thermostable mutant of T4 lysozyme Ser 117-->Phe.

The T4 lysozyme mutant Ser 117-->Phe was isolated fortuitously and found to be more thermostable than wild-type by 1.1-1.4 kcal/mol. In the wild-type structure, the side chain of Ser 117 is in a sterically restricted region near the protein surface and forms a short hydrogen bond with Asn 132. The crystal structure of the S117F mutant shows that the introduced Phe side chain rotates by about 150 degrees about the C alpha-C beta bond relative to wild type and is buried in the hydrophobic core of the protein. Burial of Phe 117 is accommodated by rearrangements of the surrounding side chains of Leu 121, Leu 133, and Phe 153 and by main-chain shifts, which result in a minimal increase in packing density. The benzyl rings of Phe 117 and Phe 153 form a near-optimal edge-face interaction in the mutant structure. This aromatic-aromatic interaction, as well as increased hydrophobic stabilization and elimination of a close contact in the wild-type protein, apparently compensate for the loss of a hydrogen bond and the possible cost of structural rearrangements in the mutant. The structure illustrates the ability of a protein to accommodate a surprisingly large structural change in a manner that actually increases thermal stability. The mutant has activity about 10% that of wild-type, supportive of the prior hypothesis (Grütter, M.G. & Matthews, B.W., 1982, J. Mol. Biol. 154, 525-535) that the peptidoglycan substrate of T4 lysozyme makes extended contacts with the C-terminal domain in the vicinity of Ser 117.

Amino Acid Sequence↗

PubMed1993

Familial effects of prostate and other cancers on lifetime breast cancer risk.

Lifetime probabilities of developing breast cancer were calculated for first-degree female relatives of three groups of breast cancer patients: 114 with bilateral cancer, 186 unselected, and 88 males. The patients were classified according to whether they had a family history of prostate, endometrial, or ovarian cancer, or no family history of these cancers. In families of unselected female and male patients with no family history of prostate, endometrial, or ovarian cancer, the lifetime probability of developing breast cancer was 11.4%. The risk increased slightly to 13.5% when these other cancers may or may not have present (i.e., they were ignored, which is the usual method in computing risks) and increased further to 25.5% when prostate, endometrial, or ovarian cancer was present in the family. In families of patients with bilateral cancer the respective risks were 10.9%, 17.3%, and 34.4%. A family history of prostate cancer increased lifetime risk consistently in each of the groups, to 29.0% in the unselected and male groups and to 38.2% in the bilateral group. Endometrial cancer increased risk only in the bilateral group (to 41.8%) as did ovarian cancer (to 54.6%). Increased risk of breast cancer with a family history of endometrial or ovarian cancer appeared to be influenced by families with hereditary breast-ovarian cancer or the cancer family syndrome. The results indicate that prostate cancer, and endometrial and ovarian cancers in some families, can significantly increase breast cancer risk and should be taken into account when counseling women about their breast cancer risk.

Adult↗

PubMed1993

Skull base approaches to complex cerebral aneurysms.

The authors used skull base approaches to improve the surgical treatment of cerebral aneurysms. These approaches facilitate aneurysm surgery by allowing early proximal and distal vascular control, shortening and widening of the operative field, increasing the range of the surgeon's operative view and motion, and alleviating brain retraction. Twenty-two patients with ruptured giant or complex aneurysms were operated upon acutely using skull base approaches appropriate for their location: (1) the orbitocranial approach for anterior circulation, ophthalmic artery, and intracavernous lesions (n = 10); (2) the orbitozygomatic approach for aneurysms of the upper third of the basilar artery (n = 6); (3) the petrosal approach for aneurysms of the middle third of the basilar artery (n = 2); and (4) the far lateral-transcondylar approach for vertebrobasilar aneurysms (n = 4). Clipping and dissection of the aneurysms was facilitated by the skull base approaches. No surgical mortality occurred in this series of patients; transient cranial nerve paresis was the only morbidity related to the approaches. We compare the three-dimensional spatial geometry of skull base and conventional approaches, and discuss the advantages and nuances of skull base approaches.

Adult↗

PubMed1993

An epitope on the surface envelope glycoprotein (gp130) of simian immunodeficiency virus (SIVmac) involved in viral neutralization and T cell activation.

SIVmac infection of macaques is an important animal model for HIV infection and AIDS; this model is being utilized for development of antiviral therapies and vaccines. In the present article, we sought to identify neutralization epitopes of SIVmac envelope surface glycoprotein (gp130). Algorithms were used to predict antigenicity of specific regions. Four regions from the primary amino acid sequence of the viral surface glycoprotein were selected. A synthetic peptide representing one of these regions (414-434) induced virus-neutralizing antibodies in mice; in addition, this peptide induced T cell-proliferative responses in macaques. To address the in vivo relevance of these observations, we demonstrated that experimentally infected macaques produce antibodies to the neutralization epitope. In addition, rhesus macaques protected against infection by an inactivated SIV vaccine develop antibodies that bind to peptide 414-434. These observations demonstrate that the region that includes the sequence 414-434 in the fourth variable domain (V4) of SIVmac gp130 contains both a linear neutralization epitope and a T cell epitope.

AIDS Vaccines↗

PubMed1993

Blood pressure during sustained inhibitory breathing in the natural environment.

Previous studies reported that breathing frequency of laboratory dogs decreased preceding the onset of an avoidance task and that this decrease was accompanied by increases in blood pressure and decreases in heart rate. Low frequency/normal tidal volume breathing has also been observed in ambulatory humans, but the cardiovascular concomitants of this inhibitory breathing pattern remain to be determined. The present study recorded blood pressure and heart rate in humans during periods of inhibitory breathing in the natural environment. Systolic and mean pressure were higher during inhibitory breathing than at other times, but no differences in diastolic pressure or heart rate were observed. Inhibitory breathing was differentially associated with the workplace and with social situations. Thus, major components of a physiological pattern that predisposes laboratory animals to sodium-sensitive experimental hypertension have now been observed to covary in ambulatory humans. Whether inhibitory breathing in the natural environment is a correlate or a cause of elevated blood pressure remains to be determined.

Adult↗

PubMed1993

Use of vascularized fat from the rectus abdominis myocutaneous free flap territory to seal the dura of basicranial tumor resections.

Resection of large skull base tumors may sometimes result in extirpation defects that are not amenable to local tissue closure. Patients with these tumors require free tissue transfer for closure of the intracranial space after basicranial tumor extirpation. The deep inferior epigastric artery supplies the rectus abdominis muscle and the skin and subcutaneous tissue of the lower abdomen. The closure of massive, central defects can be performed with a free flap designed from the ample rectus abdominis vascular territory. This free tissue donor site has abundant and reliable well-vascularized skin and subcutaneous tissue that can be customized to seal these tenuous areas and provide three-dimensional reconstruction. We have modified the rectus abdominis myocutaneous free flap in seven patients for reconstruction of the skull base. The subcutaneous fat was sculptured to form a soft, vascularized "cork" and was used for obliteration of the irregular deep portions of defects at the midcranial base against the repaired or unrepaired dura. All patients who had the vascularized fat used to obliterate the deep space had successful closure of the defect without cerebral spinal fluid leak. There were two wound infections and one donor-site hernia in this group. The judicious use of the vascular territory of the deep inferior epigastric vessels can accomplish secure three-dimensional reconstruction of the skull base. The flap can be reliably transferred, and the vascularized subcutaneous fat can be used to sequester and seal the dura repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1993

Refinements using free-tissue transfer for complex cranial base reconstruction.

Resection of skull base tumors may sometimes result in massive extirpation defects that are not amenable to local tissue closure. Closure of large basicranial defects can be performed with either a myocutaneous, a deepithelialized myocutaneous, or a simple muscle free flap designed from the ample rectus abdominis vascular territory. This free-tissue donor site has abundant and reliable well-vascularized tissue that can easily be customized to seal these tenuous areas. The rectus abdominis muscle and its vascularized territory were used in 18 of 19 consecutive patients at our center to close basicranial ablation defects. Of these, 6 were rectus abdominis muscle flaps, 5 were myocutaneous rectus abdominis flaps, and 7 were deepithelialized rectus abdominis muscle flaps. All free flaps survived. The intracranial space was sealed successfully in all but one patient. This patient underwent reconstruction with a muscle free flap and had a postoperative cerebrospinal fluid leak. This complication could have been avoided by using a deepithelialized myocutaneous flap to obliterate the central dead space with the vascularized subcutaneous fat. Two patients experienced minor wound infections, and one had a subdural abscess that was fully contained by a free flap placed over the duraplasty. One patient had a donor-site hernia. There was no incidence of meningitis. Knowledge of the anatomy of the vascular territory of the deep inferior epigastric vessels can be used judiciously to secure three-dimensional reconstruction of the skull base. The donor site supplies ample tissue for reconstruction and allows individual tailoring for obliteration of geometrically complex extirpation defects in and around the cranial base without the need to reposition the patient.

Adolescent↗

PubMed1993

Normal laparoscopic anatomy of the bovine abdomen.

Three laparoscopic procedures were performed on each of 6 adult Jersey cows in the first trimester of gestation to describe normal laparoscopic anatomy of the bovine abdomen. Also, a technique for laparoscopy of the cranioventral portion of the abdomen was described. Right paralumbar fossa, left paralumbar fossa, and cranioventral midline laparoscopy were performed 72 hours apart of each cow. Physical examination findings, CBC, serum biochemical analysis, and peritoneal fluid analysis before and 72 hours after the first surgery were used to assess the effects of the procedures on the cows. Exploratory celiotomy was performed 2 weeks after the last laparoscopy. The cows were then reexamined 6 weeks after the last procedure. The t-test for paired data was used for statistical analysis; the level of significance was P < 0.05. Laparoscopy was performed without complication in all cows. Adverse effects of laparoscopy, individually or serially, were not observed. Significant differences were not found between CBC, serum biochemical, and peritoneal fluid variables taken before and 72 hours after surgery.

Abdomen↗

PubMed1993

Abdominal pain associated with an umbilical abscess in a llama.

A 3-month-old llama with a presenting complaint of lethargy, anorexia, and a painful, distended abdomen was evaluated. The llama had intermittently strained to defecate during the 3 days prior to admission. Physical examination results, hematologic data and lateral abdominal radiographs were used to diagnose a large umbilical abscess, which was causing a partial obstruction of the gastrointestinal tract. Under general anesthesia, 3 liters of purulent exudate were drained from the abscess. The abscess cavity was then lavaged with saline solution and its capsule was marsupialized to the skin. Cultures of the abscess content yielded Proteus sp, Streptococcus equisimilis, and Clostridium septicum. Two days after surgery, the llama was drinking, eating, and passing feces. The abscess was lavaged daily for a total of 11 days. Six months after surgery, the llama was the same size as other llamas of the same age, and the owners were pleased with the cosmetic appearance of the ventral abdomen. Umbilical abscesses can vary in size and clinical presentation; they should be recognized as a possible cause of abdominal pain with a potential for causing intestinal obstruction in llamas.

Abdominal Pain↗

PubMed1993

Posterior internal auditory canal closure following the retrosigmoid approach to the cerebellopontine angle.

The retrosigmoid approach is utilized in a variety of cerebellopontine angle and internal auditory canal procedures. Drill curettage of the posterior internal auditory canal enhances lateral exposure, however, this step may also increase the patient's risk for postoperative cerebrospinal fluid (CSF) otorrhea. Obliteration of perilabyrinthine air cells is technically difficult and muscle graft displacement frequently occurs. A technique for posterior petrous dural flap stabilization of a temporalis muscle plug has proved successful in decreasing the risk of postoperative CSF fistula following retrosigmoid surgery. Temporal bone air-cell anatomy, as it relates to retrosigmoid, posterior internal auditory canal surgery is reviewed. Our technique for internal auditory canal closure, with bone wax, bone paté, muscle grafts, and petrous ridge dural flaps is outlined.

Cerebellopontine Angle↗

PubMed1992

Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22.

Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma.

Adolescent↗

PubMed1992

Familial versus sporadic breast cancer.

BACKGROUND: Studies comparing patients with familial and sporadic breast cancer have indicated that a family history of the disease can increase a woman's risk for having the disease twofold to threefold and that patients with familial breast cancer have a younger age at diagnosis and have a higher frequency of bilateral disease than those with sporadic breast cancer. Also, at least four types of breast cancers have been shown to be inherited. These findings led to the hypothesis that familial and sporadic breast cancer are the consequence of two biologically distinct mechanisms. METHODS: A two-step mutation model proposed by Knudson in 1971 provides a link between the molecular mechanisms underlying familial and sporadic breast cancer. According to this model, both cancers involve the same genomic change in homologous chromosomes. The only difference is that the first mutation is inherited and the second is somatic in familial cancer, whereas in sporadic cancer both mutations are somatic. Mutation is used in a broad sense and refers to either a point mutation at a specific locus or the loss of a locus by deletion or nondysfunction. RESULTS: This model has been shown to apply to several childhood and adult cancers, including breast cancer. Based on this model, patients with familial breast cancer will have their disease earlier in life and will have more bilateral cancer than patients with sporadic breast cancer. Moreover, the two types of patients should show no differences in clinicopathologic characteristics because both types involve the same genomic change and the pathogenesis of both types should be the same, thus arguing against the early hypothesis that patients with familial and sporadic breast cancer are the consequence of biologically distinct mechanisms. CONCLUSIONS: Breast cancer appears to involve the cumulative effect of several genetic lesions involving the activation of oncogenes and the inactivation of tumor-suppressor genes. Which genes are involved specifically as causative factors of breast cancer (the inherited gene or genes) and which are important somatically in its continued development and progression (oncogenes and tumor-suppressor genes) requires additional study.

Adult↗

PubMed1992

Breast cancer risks in relatives of male breast cancer patients.

BACKGROUND: Previous studies have provided conflicting results concerning the familial effect of male breast cancer on breast cancer risks in female relatives. PURPOSE: We studied breast cancer risks in first-degree relatives of male patients and compared them with relatives of female patients. METHODS: Our study included 88 consecutively ascertained male patients and 320 of their first-degree relatives as well as 186 consecutively ascertained female patients and 633 of their first-degree relatives. Observed numbers of breast cancers in relatives were compared with the expected number derived from the Connecticut Tumor Registry. Multiple logistic regression analysis was also performed. RESULTS: Relatives of male patients exhibited a significant twofold increased risk when compared with expected rates and no difference in risk when compared with that of relatives of female patients. Prostate cancer in the family of a male patient resulted in a significant fourfold increased breast cancer risk compared with a risk of 1.4 in families with no history of prostate cancer. A family history of lung cancer, colon cancer, or melanoma had no effect on increasing risks of breast cancer. CONCLUSION: The familial effect of male breast cancer is the same as that of female breast cancer. IMPLICATIONS: Any estimates of breast cancer risk provided to individuals should also consider the occurrence of prostate cancer in the family, since prostate cancer appears capable of at least doubling the underlying twofold risk.

Age Factors↗

PubMed1992

Social and behavioral factors associated with episodes of inhibitory breathing.

Previous research has shown that episodes of inhibitory breathing, characterized by low-frequency breathing, occur both in laboratory animals during intervals preceding avoidance tasks and in humans in the natural environment. The present study investigated social and behavioral factors accompanying episodes of inhibitory breathing that occur in the natural environment. Breathing frequency and tidal volume of ambulatory subjects were monitored via inductive plethysmography. Information concerning location, social environment, behavior, and mood was self-recorded in a computerized diary. The percentage of episodes of inhibitory breathing was found to be significantly greater in social situations than when subjects were alone. Additional analyses eliminated talking as an explanation for these effects. Inhibitory breathing was more frequent when subjects were sedentary rather than active, and inhibitory breathing was not associated with changes in mood or appraisal. Additional research is needed to determine the nature of the social interactions that elicit inhibitory breathing, its physiological concomitants, and its long-term health implications.

Adult↗

PubMed1992

Reliability of the serial sampling technique for determination of gastric emptying.

The purpose of this study was to determine if gastric emptying data obtained in one trial (using the intubation and aspiration method) is representative of that obtained in subsequent trials or on repeated days. Nine healthy adults consumed a volume of water (5.5 ml/kg body weight) which contained a nonabsorbable marker. Following a fifteen-minute rest period, the stomach contents were aspirated using a 50 ml syringe. This procedure was repeated three additional times on the same day with a fifteen minute interval separating each trial. On two other days the identical procedures were performed. A significant daily variation was found for residue volume, gastric secretion, and percent of original drink emptied. However, no significant difference between trials within a day was found for the residue volume, gastric secretion, and percent of original drink emptied. Generalizability coefficients, which are "reliability-like" coefficients, were also calculated. These coefficients indicate that a combination of at least 2 days with at least 2 trials/day should be used in order to obtain reliable gastric emptying data.

Adult↗

PubMed1992

Ambulatory monitoring of respiration: inhibitory breathing in the natural environment.

Because previous work found that sustained inhibitory breathing (i.e., low frequency breathing without increased tidal volume) can occur in laboratory animals under conditions of behavioral stress, this study sought to determine whether a comparable respiratory pattern could be observed in ambulatory human subjects in their natural environments. Tidal volume, breathing frequency, and minute ventilation were monitored continuously during 24-hour sessions via inductive plethysmography and a portable microprocessor. Mean tidal volume and minute ventilation were significantly higher during the daytime than at night for all subjects. However, mean breathing frequency was not consistently higher during the daytime, because episodes of low frequency breathing offset episodes of high breathing frequency. Tidal volume during low frequency breathing was comparable to that observed during medium or high frequency breathing. Thus, low frequency breathing was indicative of low minute ventilation. The eliciting stimuli, physiological concomitants, and relevance to health of this energetically inefficient breathing pattern remain to be determined.

Adult↗