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Biomedical subjects

J C Watson

Publications and source records attributed to J C Watson.

At least 19 recordsLinked to original sources
PubMed2007

Muscle architecture of biceps brachii, triceps brachii and supraspinatus in the horse.

Three muscles from the proximal equine forelimb were dissected in order to investigate their potential to contribute to proximal limb mechanics. Muscle mass, fibre length, tendon mass and tendon length were measured from biceps brachii, triceps brachii, supraspinatus and lacertus fibrosus (biceps lateral head mass 171-343.4 g and fibre length 0.5-0.8 cm; biceps medial head mass 283-500 g and fibre length 2.2-4 cm; biceps tendon mass 121.8-260 g and tendon length 35-44 cm; triceps long head mass 3200-6663 g and fibre length 19-26.3 cm; triceps lateral head mass 513.8-1240 g and fibre length 17.5-24 cm; triceps medial head mass 85.2-270.6 g and fibre length 9-16.8 cm; supraspinatus mass 793-1546 g and fibre length 4.7-12.4 cm; lacertus fibrosus mass 4.6-12.4 g and length 10-16 cm). Physiological cross-sectional area (PCSA) and maximum isometric force were estimated for each muscle, and moment arm measurements were taken at the shoulder and elbow joints. Biceps has a greater isometric force-generating capacity than supraspinatus. It also appears to have a larger shoulder moment arm, so could therefore have the potential to make a greater contribution to the shoulder moment than supraspinatus. Supraspinatus is likely to function primarily as a shoulder stabilizer rather than a shoulder extensor. Biceps also functions as an elbow flexor and data here indicate that it has a greater PCSA and isometric force-generating capacity than its antagonist triceps brachii. Calculation of tendon forces showed that the biceps tendon can withstand much greater forces than lacertus fibrosus. This study will enable further investigation into the interaction between energy recycling in elastic tissues and the generation and absorption of mechanical work by adjacent muscle groups in the equine forelimb.

Animals↗
PubMed2005

Effects of mitomycin C on glaucoma filtration capsules.

One of the leading causes of implantable device failure is build up of scar tissue on the device. Approaches to address this complication range from choosing device materials that prevent cell adhesion to treatment with potent antifibrotic medications such as mitomycin C. We examined the collagen matrix around aqueous shunt implants in rabbit eyes and found the filtration capsule formed around these devices is not composed of scar tissue. Rather collagen deposition is highly organized with collagen bundles oriented along stress axes. We also examined adjacent tissue deposition in mitomycin C treated animals and found decreased vascularization, condensed collagen in Tenon's capsule with more collagen bundles less well formed than those in the control eye of the same animal. The sclera was thicker under the plate than at the opposite side of the same eye. Structural and functional evaluation correlates with the clinical paradox that patients treated with mitomycin C have lower initial pressures with adjunct drug treatment but lower success rates than the control population after 18 months.

Animals↗
PubMed2005

Differential stromal and epithelial localization of cyclooxygenase-2 (COX-2) during colorectal tumorigenesis.

The purpose of the following study is to describe the localization of COX-2 protein and COX-2 mRNA during human colorectal tumorigenesis and to identify potential cellular targets for COX-2 inhibition in chemopreventive strategies. Immunohistochemistry with digital image analysis was used to determine COX-2 protein expression in histologic sections containing synchronous normal colorectal mucosa, adenomas and carcinomas, from 17 previously untreated patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected samples from the same histologies. The stromal compartment in normal colorectal mucosa and adenomas showed higher levels of COX-2 protein expression compared to colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was significantly increased only after development of the invasive phenotype (p < .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that within the epithelium for colorectal adenomas and carcinomas. In conclusion, stromal COX-2 may be the target for chemopreventive agents in the early stages of colorectal carcinogenesis.

Adenoma↗
PubMed2002

PROGINS Alu insertion and human genomic diversity.

A polymorphic Alu element belonging to the young Ya5 subfamily of Alu repeats located in the progesterone receptor gene has been characterized. Using a polymerase chain reaction (PCR)-based assay, the genetic diversity associated with the PROGINS Alu repeat was determined in a diverse array of human populations. The level of insertion polymorphism associated with PROGINS suggests that it will be a useful marker for the study of human evolution. In addition, we determined the distribution of the PROGINS Alu insertion in two groups of women from greater New Orleans, LA with breast cancer. The PROGINS Alu insertion was not associated with breast cancer in the populations tested.

Alu Elements↗
PubMed2001

Growing vascular endothelial cells express somatostatin subtype 2 receptors.

We hypothesized that non-proliferating (quiescent) human vascular endothelial cells would not express somatostatin receptor subtype 2 (sst 2) and that this receptor would be expressed when the endothelial cells begin to grow. To test this hypothesis, placental veins were harvested from 6 human placentas and 2 mm vein disks were cultured in 0.3% fibrin gels. Morphometric analysis confirmed that 50-75% of cultured vein disks developed radial capillary growth within 15 days. Sst 2 gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the RNA from veins before culture and from tissue-matched vein disks that exhibited an angiogenic response. The sst 2 gene was expressed in the proliferating angiogenic sprouts of human vascular endothelium. The presence of sst 2 receptors on proliferating angiogenic vessels was confirmed by immunohistochemical staining and in vivo scintigraphy. These results suggest that sst 2 may be a unique target for antiangiogenic therapy with sst 2 preferring somatostatin analogues conjugated to radioisotopes or cytotoxic agents.

Animals↗
PubMed2001

Effects of nitric oxide on reactive oxygen species production and infarction size after brain reperfusion injury.

OBJECTIVE: Deleterious effects of strokes may be ameliorated when thrombolysis (i.e., with recombinant tissue plasminogen activator) restores circulation. However, reperfusion injury, mediated by oxygen free radicals (reactive oxygen species [ROS]), may limit the benefits of recombinant tissue plasminogen activator treatment. We hypothesized that, during reperfusion, exogenous nitric oxide (NO) would reduce stroke size by quenching ROS. METHODS: To investigate this hypothesis, we used two in vivo ischemia-reperfusion models, i.e., autologous cerebral embolism in rabbits and filament middle cerebral artery occlusion in rats. Using these models, we measured ROS levels (rabbit model) and stroke volumes (rat model) in response to transient ischemia, with and without intracarotid administration of ultrafast NO donor proline NO (proliNO). RESULTS: In the rabbit cerebral embolism model, intracarotid administration of proliNO (10(-6) mol/L) (n = 6) during reperfusion decreased free radical levels from 538 +/- 86 nmol/L in the vehicle-treated group (n = 7) to 186 +/- 31 nmol/L (2,3'-dihydroxybenzoic acid; P < 0.001) and from 521 +/- 86 nmol/L (n = 7) to 201 +/- 39 nmol/L (2,5'-dihydroxybenzoic acid; P < 0.002). In the rat middle cerebral artery occlusion model, intracarotid administration of proliNO (10(-5) mol/L) (n = 10) during reperfusion reduced the brain infarction volume from 256 +/- 48 mm3 in the vehicle-treated group (n = 8) to 187 +/- 41 mm3 (P < 0.005). In both experimental groups, intracarotid infusion of proliNO did not affect regional cerebral blood flow, mean arterial blood pressure, or brain and body temperatures. CONCLUSION: The beneficial effects of early restoration of cerebral circulation after cerebral ischemia were enhanced by intracarotid infusion of proliNO, most likely because of ROS scavenging by NO. These findings suggest the possibility of preventive treatment of reperfusion injury using NO donors.

Animals↗
PubMed2000

Alliance ruptures and repairs in experiential therapy.

The formation and maintenance of a positive working alliance is fundamental to the success of experiential therapy. Experiential therapists face a special challenge insofar as they must constantly consider whether to direct the therapeutic process more actively or remain more closely within the clients' own frame of reference. This requires that experiential therapists be acutely aware of the alliance with their clients on a moment-to-moment basis during the session. In this article ruptures to the alliance, comprising breakdowns In the agreement between clients and therapists as to the goals and tasks of therapy during the early and middle phases of treatment, are identified and explored. As ruptures are often covert processes, methods of detecting their occurrence during the session are presented. Finally, experiential techniques for forging, maintaining, and repairing the alliance between clients and therapists are discussed and illustrated.

Cognitive Behavioral Therapy↗
PubMed2000

Pancreatic cancer.

Optimal therapy for pancreatic adenocarcinoma requires surgical removal with tumor-free margins. Superior outcomes have been reported for high-volume centers incorporating a multidisciplinary approach. Postoperative ("adjuvant") chemotherapy and radiation should be considered in patients with successfully resected primary tumors. Combined modality treatment with chemotherapy and radiation should be considered for locally advanced, unresectable tumors. Gemcitabine can provide symptom relief and a modest improvement in survival for patients with metastatic disease. Strict attention to relief of symptoms such as pain, depression, anorexia/cachexia, and jaundice is essential in all patients with pancreatic cancer. All patients with pancreatic cancer should be encouraged to enter clinical trials of new therapies, given that long-term survival for all stages remains poor.

Adenocarcinoma↗
PubMed2000

Neurosurgical implications of Carney complex.

OBJECT: The authors present their neurosurgical experience with Carney complex. Carney complex, characterized by spotty skin pigmentation, cardiac myxomas, primary pigmented nodular adrenocortical disease, pituitary tumors, and nerve sheath tumors (NSTs), is a recently described, rare, autosomal-dominant familial syndrome that is relatively unknown to neurosurgeons. Neurosurgery is required to treat pituitary adenomas and a rare NST, the psammomatous melanotic schwannoma (PMS), in patients with Carney complex. Cushing's syndrome, a common component of the complex, is caused by primary pigmented nodular adrenocortical disease and is not secondary to an adrenocorticotropic hormone-secreting pituitary adenoma. METHODS: The authors reviewed 14 cases of Carney complex, five from the literature and nine from their own experience. Of the 14 pituitary adenomas recognized in association with Carney complex, 12 developed growth hormone (GH) hypersecretion (producing gigantism in two patients and acromegaly in 10), and results of immunohistochemical studies in one of the other two were positive for GH. The association of PMSs with Carney complex was established in 1990. Of the reported tumors, 28% were associated with spinal nerve sheaths. The spinal tumors occurred in adults (mean age 32 years, range 18-49 years) who presented with pain and radiculopathy. These NSTs may be malignant (10%) and, as with the cardiac myxomas, are associated with significant rates of morbidity and mortality. CONCLUSIONS: Because of the surgical comorbidity associated with cardiac myxoma and/or Cushing's syndrome, recognition of Carney complex has important implications for perisurgical patient management and family screening. Study of the genetics of Carney complex and of the biological abnormalities associated with the tumors may provide insight into the general pathobiological abnormalities associated with the tumors may provide insight into the general pathobiological features of pituitary adenomas and NSTs.

Acromegaly↗
PubMed2000

Neuroprotection by the stable nitroxide Tempol during reperfusion in a rat model of transient focal ischemia.

OBJECT: The use of thrombolytic agents in the treatment of stroke has yielded surprisingly modest success, possibly because of reperfusion injury mediated by reactive oxygen species (ROS). Therefore, scavenging ROS may be of therapeutic value in the treatment of stroke. Nitroxides are low-weight superoxide dismutase mimics, which allows them to act as cell-permeable antioxidants. In this study the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol) is investigated to determine its ability to reduce reperfusion injury. METHODS: Male Sprague-Dawley rats weighing between 280 g and 350 g underwent middle cerebral artery occlusion with an intraluminal suture for 60 minutes. Regional cerebral blood flow, blood pressure, cerebral temperature, and rectal temperature were monitored during the procedure. After reperfusion, the animals were randomized to groups receiving blinded intravenous administration of either Tempol (10 mg/kg; eight animals) or vehicle (eight animals) over the first 20 minutes of reperfusion (Study I). In a second study to determine dose dependency, animals were randomized to groups receiving Tempol (20 mg/kg; eight animals), low-dose Tempol (5 mg/kg; eight animals), or vehicle (eight animals; Study II). The rats were killed after 4 hours of reperfusion, and brain sections were stained with 2,3,5 triphenyltetrazolium chloride. Infarct volumes were measured using digital imaging. Animals receiving Tempol had significantly reduced infarct volumes at doses of 20 mg/kg and 10 mg/kg compared with controls (49.01+/-18.22% reduction [p = 0.003] and 47.47+/-34.57 [p = 0.02], respectively). No significant differences in the physiological variables measured were observed between groups. CONCLUSIONS: Tempol provides significant neuroprotection after reperfusion in a rat model of transient focal ischemia. These results support the importance of ROS in reperfusion injury and encourage further study of this molecule as a therapeutic agent following thrombolysis.

Animals↗
PubMed2000

Resection of suprasellar tumors by using a modified transsphenoidal approach. Report of four cases.

Generally accepted contraindications to using a transsphenoidal approach for resection of tumors that arise in or extend into the suprasellar region include a normal-sized sella turcica, normal pituitary function, and adherence of tumor to vital intracranial structures. Thus, the transsphenoidal approach has traditionally been restricted to the removal of tumors involving the pituitary fossa and, occasionally, to suprasellar extensions of such tumors if the sella is enlarged. However, conventional transcranial approaches to the suprasellar region require significant brain retraction and offer limited visualization of contralateral tumor extension and the interface between the tumor and adjacent structures, such as the hypothalamus, third ventricle, optic apparatus, and major arteries. In this paper the authors describe successful removal of suprasellar tumors by using a modified transsphenoidal approach that circumvents some of the traditional contraindications to transsphenoidal surgery, while avoiding some of the disadvantages of transcranial surgery. Four patients harbored tumors (two craniopharyngiomas and two hemangioblastomas) that arose in the suprasellar region and were located either entirely (three patients) or primarily (one patient) within the suprasellar space. All patients had a normal-sized sella turcica. Preoperatively, three of the four patients had significant endocrinological deficits signifying involvement of the hypothalamus, pituitary stalk, or pituitary gland. Two patients exhibited preoperative visual field defects. For tumor excision, a recently described modification of the traditional transsphenoidal approach was used. Using this modification, one removes the posterior portion of the planum sphenoidale, allowing access to the suprasellar region. Total resection of tumor was achieved (including absence of residual tumor on follow-up imaging) in three of the four patients. In the remaining patient, total removal was not possible because of adherence of tumor to the hypothalamus and midbrain. One postoperative cerebrospinal fluid leak occurred. Postoperative endocrinological function was worse than preoperative function in one patient. No other new postoperative endocrinological or neurological deficits were encountered. This study demonstrates the feasibility of using a modified transsphenoidal approach for resection of certain suprasellar, nonpituitary tumors.

Adolescent↗
PubMed1999

Intraoperative gamma detection of 125I-lanreotide in women with primary breast cancer.

BACKGROUND: Somatostatin receptors are present in most human breast cancers. We performed a pilot trial of intraoperative tumor-gamma detection using the radiolabeled somatostatin analog 125I-lanreotide in 13 women with 14 primary breast carcinomas. METHODS: All patients were given 125I-lanreotide intravenously before surgery. Patients underwent lumpectomy, and postresection margins were evaluated with the gamma probe. Axillary dissection specimens were evaluated ex vivo. RESULTS: Seven of 13 women had gamma probe-positive or clinically suspicious margins re-excised at the time of lumpectomy. Four of six probe-positive margins were histologically positive, and two of six probe-positive margins were histologically negative; a single clinically suspicious margin was histologically positive. A total of 270 axillary lymph nodes were evaluated ex vivo by gamma probe and histology. McNemar's contingency tests demonstrated a highly statistical correlation between histology and gamma probe counts (P < .0001). CONCLUSIONS: The overall accuracy of nodal evaluation with 125I-lanreotide/intraoperative gamma detection was 77%; the negative predictive value of this technique was 97%, however. This technique predicted the presence of tumor in 20% of axillary lymph nodes that were negative by routine histology. This technique appears safe and is able to detect positive tumor resection margins and accurately predict axillary lymph node negativity. Further trials of this technique are required to validate its utility.

Aged↗
PubMed1999

Photoregulated expression of the PsPK3 and PsPK5 genes in pea seedlings.

The PsPK3 and PsPK5 genes of the garden pea encode protein-serine/threonine kinases whose catalytic domains are closely related to known signal transducing kinases from animals and fungi. The PsPK3 polypeptide is predicted to be located in the nucleus, whereas PsPK5 is a homologue of NPH1, the probable blue light receptor for phototropism from Arabidopsis. We found previously that when etiolated pea seedlings are illuminated with continuous white light, PsPK3 and PsPK5 transcript levels within apical buds decline substantially, reaching their minimum levels within one day of exposure to light. The role of light in regulating the expression of the PsPK3 and PsPK5 genes was investigated further. To gain insight into the rapidity with which expression changes, 6-day old, dark-grown pea seedlings were transferred to continuous white light, and PsPK3 and PsPK5 RNA levels monitored over the ensuing 24 h. While transcripts from the RbcS gene family increase, the PsPK3 and PsPK5 mRNAs decline rapidly to their minimum levels. PsPK5 mRNA declines 10-fold in ca. 2 h, whereas PsPK3 mRNA declines 4-fold in ca. 8 h. We used single pulses of light to elucidate which photoreceptor triggers the negative regulation of PsPK3 and PsPK5 gene expression. To assess phytochrome involvement, etiolated seedlings were treated with single pulses of red light, red followed by far-red light, or far-red light alone. RbcS induction by a red light pulse is reversible with a subsequent far-red light pulse, clearly showing that phytochrome mediates its induction. Likewise, RbcS expression is induced with a single pulse of blue light or a dichromatic pulse of red+blue light. However, none of these pulses trigger the PsPK3 and PsPK5 mRNA levels to decline. Given the lack of effectiveness of light pulses, etiolated seedlings were transferred to continuous light of three different qualities to determine the spectral sensitivity of PsPK3 and PsPK5 gene expression. Exposure to continuous red, continuous far-red, or continuous blue light causes the PsPK3 and PsPK5 mRNAs to decline and transcripts from the RbcS and Cab gene families to increase. One likely explanation is that phytochrome A mediates the responses of these genes to continuous far-red light. The effectiveness of continuous red light and blue light in triggering the reduction in PsPK3 and PsPK5 mRNA levels and the increase in RbcS and Cab mRNAs may imply the participation of additional phytochromes and/or cryptochromes. Thus, the PsPK3 and PsPK5 genes exhibit responsiveness to continuous light, but a lack of responsiveness to single light pulses that is unusual, and perhaps unique, among light-regulated genes.

Arabidopsis Proteins↗
PubMed1999

Extrapituitary parasellar microadenoma in Cushing's disease.

Negative sellar exploration (despite the results of endocrine evaluation indicating Cushing's disease), the high incidence of failure of total hypophysectomy, and remission of Cushing's syndrome after unsuccessful hypophysectomy and sellar irradiation suggest that the etiology of refractory Cushing's disease, in some patients, lies near the sella but not in the pituitary gland. We present 5 patients, out of 626 who received surgery for Cushing's disease, in whom an ACTH-secreting extrapituitary parasellar adenoma was identified: 2 after unsuccessful total hypophysectomy for the treatment of refractory Cushing's disease, 2 after unsuccessful hemihypophysectomy (the first, 2 yr before treatment at the NIH for Nelson's syndrome; and the second, with recurrent Cushing's disease 5 yr after negative transsphenoidal exploration), and 1 with a preoperative diagnosis of an intraclival microadenoma, which was cured by resection of the tumor. In all cases, an extrapituitary parasellar microadenoma was confirmed unequivocally as the cause of the disease, by negative pathology of the resected pituitary gland (patients 1, 2, 3, and 5), and/or the remission of the disease after selective resection of the extrasellar adenoma (patients 3, 4, and 5). Three of 5 patients had a partial empty sella. These patients support the thesis that ACTH-secreting tumors can arise exclusively from remnants of Rathke's pouch, rather than from the adenohypophysis (anterior lobe or pars tuberalis of the pituitary gland) and can be a cause of Cushing's disease. In the sixth presented case, an extrapituitary tumor was suspected at surgery after negative pituitary exploration, but serial sections of the hemihypophysectomy specimen revealed a microscopic focus of tumor at the margin of the resected gland. This case demonstrates the importance of negative pituitary histology to establish the presence of an extrapituitary parasellar tumor as an exclusive source of ACTH, and it supports the value of clinical outcome to establish the diagnosis with selective adenomectomy of an extrapituitary parasellar tumor. In patients with negative pituitary magnetic resonance imaging, especially in the presence of a partial empty sella, the diagnostic and surgical approach in Cushing's disease should consider the identification and resection of extrapituitary parasellar adenoma, which can avoid total hypophysectomy, as was possible in 3 of our 5 patients.

Adenoma↗
PubMed1999

Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck.

Angiogenesis has been linked to increased metastasis formation and decreased overall survival in patients with various tumors, including and neck squamous cell carcinomas (HNSCC). Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. In the present study, we evaluated VEGF expression and microvessel density (MVD), a quantitative means of angiogenesis, in both experimental and clinical models of HNSCC. Analysis of VEGF RNA expression in cell lines of keratinocyte origin [HNSCC, facial skin squamous cell carcinoma (SCC), and transformed but nontumorigenic keratinocytes] and normal skin keratinocytes revealed two VEGF transcripts corresponding to proteins of 165 and 121 amino acids in length, with the transcript for the 165-amino acid species predominating. Six of eight SCC cell lines showed increased levels of one or both transcripts, and seven SCC cell lines and the transformed keratinocyte cell line showed increased protein expression. We then evaluated VEGF protein expression in human head and neck specimens containing normal epithelium (n = 10), dysplasia or carcinoma in situ (CIS; n = 15), early invasive SCCs (n = 9), advanced primary SCCs (n = 10), lymph node metastases (n = 3), and s.c. tumors or cysts (n = 7) formed in severe combined immunodeficient mice. Intense VEGF staining was found in the majority of advanced primary SCCs, lymph node metastases, and human SCCs in severe combined immunodeficient mice, whereas no dysplasia, CIS, or early SCCs showed intense immunostain. A highly significant increase (P = 0.0001) in VEGF expression was seen in the advanced SCC versus dysplasias and CIS lesions, as was the difference between SCC versus normal epithelium from nonsmokers (P = 0.01). VEGF expression in advanced primary cancers was greater (P = 0.002) and, in early cancers, marginally greater (P = 0.05) than adjacent normal mucosa. MVD increased with the progression of preinvasive disease (P = 0.04). VEGF expression and MVD (both, P = 0.003) were directly associated with tumor aggressiveness in experimental tumors. These findings suggest a role for VEGF in both clinical and experimental HNSCC.

Adult↗