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Biomedical subjects

G Wilson

Publications and source records attributed to G Wilson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Recovery of sperm production following radiation therapy for Hodgkin's disease after induction chemotherapy with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP).

PURPOSE: The effect on human male fertility of radiotherapy following chemotherapy for the treatment of Hodgkin's disease (HD) is unknown. The impact of radiation therapy, given after mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) chemotherapy, on sperm production is the focus of this study. PATIENTS: Serial semen analyses were performed on 34 patients with HD Stages I-III before NOVP chemotherapy, after chemotherapy prior to radiation, and after radiation therapy. The most inferior radiation portals for patients were: mantle, 1 patient; paraaortic-spleen, 3 patients; upper abdomen, 24 patients; abdominal spade, 4 patients; and pelvic, 2 patients. Testicular radiation dose measurements were available for 20 of these patients. RESULTS: Before the start of radiation, 90% of patients were normospermic. The magnitude of the decline in sperm counts was related to the measured testicular dose and/or radiation fields employed. The minimum postradiotherapy counts, expressed as a fraction of pretreatment counts, for the various treatment groups are as follows: paraaortic-spleen, 20%; upper abdomen, testicular dose < 30 cGy, 4%; upper abdomen, testicular dose 30-39 cGy, 0.9%; abdominal spade, 0.02%; and pelvis, 0%. The time to nadir of sperm counts averaged 4.5 months. Recovery to normospermic levels occurred in 96% of patients, with most recovering to that level within 18 months. CONCLUSION: The effect of radiation following NOVP chemotherapy on sperm counts was no greater than would be expected with radiation therapy alone. In most patients, sperm counts recovered to levels compatible with normal fertility.

Adolescent↗
PubMed2000

CT measurement of medial temporal lobe atrophy in Alzheimer's disease, vascular dementia, depression and paraphrenia.

OBJECTIVE: Measurement of medial temporal lobe atrophy (MTL) by computerised tomography (CT) may be a useful adjunct to the diagnosis of AD. The aim of this study was to assess the sensitivity, specificity, predictive values and diagnostic accuracy of CT measurement of MTL thickness for patients with probable AD, compared with a 'diseased' control group, and to correlate the measure with neuropsychological test scores. DESIGN: Cross-sectional. METHODS: One hundred subjects were prospectively recruited: 60 with probable AD (mean age 73.7 years, mean Mini-Mental State Examination [MMSE] 19.6), 17 with probable vascular dementia (VaD) (mean age 77.9 years, mean MMSE 20.9), 14 with depression (mean age 73.2 years, mean MMSE 25.7) and nine with paraphrenia (mean age 74 years, mean MMSE 25.4). Axial and temporal lobe-oriented CT brain was performed and the minimum MTL thickness was measured electronically. RESULTS: The mean minimum MTL thickness was significantly smaller in AD subjects compared to VaD (p<0.0001) and psychiatric subjects (p<0.0001). For the clinical diagnosis of probable AD, the sensitivity of the measure was 0.75, specificity 0.9, and diagnostic accuracy 0.81. For the mildest cases of AD (CDR 0.5), the sensitivity of the measure was 0.61, specificity 0.91, and diagnostic accuracy 0.81. No significant correlations with neuropsychological test scores were found. CONCLUSIONS: Temporal lobe-oriented CT imaging is a non-invasive test with good discrimination for AD. Potential uses of this technique include as an aid to diagnosis and possibly as a means of monitoring disease progression.

Aged↗
PubMed2000

Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy.

To determine whether the measurement of repeat number mutations at a minisatellite locus could detect human germline mutations induced by chemotherapy, we performed a longitudinal study of the mutation frequencies in sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reaction on small pools of DNA equivalent to 100 sperm and Southern blotting were used to screen at least 7900 sperm in each sample to quantify the mutation frequency at the minisatellite MS205 locus. Pretreatment and posttreatment semen samples were obtained at least 2 months after completion of therapy from 4 patients treated with a regimen (Novantrone, Oncovin, vinblastine and prednisone [NOVP]) that lacks alkylating agents and from three patients treated with regimens (Cytoxan, vinblastine, procarbazine and prednisone/Adriamycin, bleomycin, dacarbazine, lomustine, and prednisone [CVPP/ABDIC] or mechlorethamine, Oncovin, procarbazine and prednisone [MOPP]) containing alkylating agents. There were no effects of NOVP or CVPP/ABDIC on the mutation frequencies. In the 1 patient treated with MOPP, the treatment with the highest dose of gonadotoxic alkylating agents, there was a statistically significant increase in mutation frequency from 0.79% pretreatment to 1.14% posttreatment, indicating induction of mutations in stem spermatogonia. During-treatment semen samples obtained from 2 patients treated with ABVD, which does not contain gonadotoxic alkylating agents, and 1 with NOVP also did not show any increases above the baseline mutation frequencies, indicating no increase in the minisatellite mutation frequency in spermatocytes. Thus, measurement of repeat number changes at minisatellite MS205 appears to be able to detect induced germline mutations in human sperm. However, most chemotherapy regimens do not significantly increase this class of mutations.

Adult↗
PubMed2000

Dose-related elevations in venous pH with citrate ingestion do not alter 40-km cycling time-trial performance.

The purpose of the current investigation was to determine whether sodium citrate enhances endurance cycling performance and, if so, what dosage(s) produces this effect. Eight trained [peak power output: 362 (48) W; power:weight: 5.1 (0.4) W x kg(-1), mean (SD)] male cyclists were requested to complete four, 40-km time-trials, each separated by 3-7 days, on their own bicycles, mounted on a Kingcycle ergometer. To mimic the stochastic nature of cycle road races, the time-trials included four 500-m, four 1-km and two 2-km sprints. The experimental conditions involved the ingestion of three dosages of sodium citrate dissolved in 400 ml water: 0.2 g x kg(-1), 0.4 g x kg(-1) and 0.6 g x kg(-1) body mass (b.m.) and a placebo (calcium carbonate, 0.1 g x kg(-1) b.m.). Subjects were asked to complete both the sprints and total distance in the fastest time possible. Venous blood samples were collected before, as well as at 10-km intervals during the trials for the analysis of plasma lactate and glucose concentrations and for the measurement of blood pH and PCO2 levels. Immediately before, as well as during exercise, pH was significantly higher in the group ingesting the highest citrate dose (range 7.36-7.45) compared to the placebo (range 7.31-7.39) and the two lower citrate dosages. Despite this, no significant differences in power output (P = 0.886) or time taken to complete the 40 km (P = 0.754) were measured between the four trials. The average performance times (in min:s, with SD in parentheses) and average power output (in W) for the 40-km time-trials were: 58:46 (5:06) [265 (62) W], 60:24 (6:07) [251 (59) W], 61:47 (5:07) [243 (44) W] and 60:02 (5.05) [255 (55) W] for the 0.2, 0.4, 0.6 g x kg(-1) b.m. sodium citrate and placebo trials, respectively. There were also no significant differences measured between treatments in terms of time, power output, speed or heart rate during the 500-m, 1-km and 2-km sprints. The ingestion of increasing sodium citrate dosages before exercise produced dose-dependent changes in pH, base excess and HCO3- concentrations before and during the 40-km time-trial. However, these changes influenced neither the time-trial time nor the sprinting performance times.

Bicarbonates↗
PubMed2000

Advantages of smaller body mass during distance running in warm, humid environments.

The purpose of this study was to examine the extent to which lighter runners might be more advantaged than larger, heavier runners during prolonged running in warm humid conditions. Sixteen highly trained runners with a range of body masses (55-90 kg) ran on a motorised treadmill on three separate occasions at 15, 25 or 35 degrees C, 60% relative humidity and 15 km x h(-1) wind speed. The protocol consisted of a 30-min run at 70% peak treadmill running speed (sub-max) followed by a self-paced 8-km performance run. At the end of the submax and 8-km run, rectal temperature was higher at 35 degrees C (39.5+/-0.4 degrees C, P<0.05) compared with 15 degrees C (38.6+/-0.4 degrees C) and 25 degrees C (39.1+/-0.4 degrees C) conditions. Time to complete the 8-km run at 35 degrees C was 30.4+/-2.9 min (P<0.05) compared with 27.0+/-1.5 min at 15 degrees C and 27.4+/-1.5 min at 25 degrees C. Heat storage determined from rectal and mean skin temperatures was positively correlated with body mass (r=0.74, P<0.0008) at 35 degrees C but only moderately correlated at 25 degrees C (r=0.50, P<0.04), whereas no correlation was evident at 15 degrees C. Potential evaporation estimated from sweat rates was positively associated with body mass (r=0.71, P<0.002) at 35 degrees C. In addition, the decreased rate of heat production and mean running speed during the 8-km performance run were significantly correlated with body mass (r=-0.61, P<0.02 and r=-0.77, P<0.0004, respectively). It is concluded that, compared to heavier runners, those with a lower body mass have a distinct thermal advantage when running in conditions in which heat-dissipation mechanisms are at their limit. Lighter runners produce and store less heat at the same running speed; hence they can run faster or further before reaching a limiting rectal temperature.

Blood Volume↗
PubMed2000

An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer's disease.

This review summarizes recent advancements in our understanding of the potential role of the amyloid beta protein in Alzheimer's disease. It also discusses the significance of amyloid beta in initiating the generation of partially reduced oxygen species and points out their role in damaging essential macromolecules in the CNS which leads to neuronal dysfunction and loss. Recently acquired experimental data links these destructive oxidative processes with some neurodegenerative aspects of Alzheimer's disease. The experimental findings related to the free radical scavenging and antioxidative properties of melatonin are tabulated and its efficacy and the likely mechanisms involved in its ability to reduce neuronal damage mediated by oxygen-based reactive species in experimental models of Alzheimer's disease are summarized. Besides the direct scavenging properties and indirect antioxidant actions of melatonin, its ability to protect neurons probably also stems from its antiamyloidogenic properties. Melatonin is also unique because of the ease with which it passes through the blood-brain barrier.

Alzheimer Disease↗
PubMed2000

African American grandmothers' perceptions of caregiver concerns associated with rearing adolescent grandchildren.

In 1996, grandparents were the sole providers of care for 269,000 grandchildren. Research findings indicate that grandmothers are usually the primary caretakers of grandchildren. Previous issues associated with raising grandchildren vary, but usually relate to the grandparents' health, financial concerns, or lack of social support. This qualitative descriptive study was designed to describe African American grandmothers' perceptions about the burdens of raising adolescent grandchildren. Using this approach, the researchers were able to study the richness and diversity of the grandmothers' perceptions. Data were collected from 35 grandmothers through a focus group (n = 7) and during a 4-day intervention research study (n = 28) entitled "Grandmother-Grandchild Health Promotion Program." Numerous concerns were voiced by both groups, but those stated most frequently were associated with the well-being of grandchildren (grandchildren's sexual behavior, potential drug use, and potential risk of encountering violence) and relational conflicts with adult children. Unexpected findings were the absence of stated concerns associated with the grandmothers' financial situation or health. Recommendations for intervention, clinical practice, and research are discussed.

Adolescent↗
PubMed2000

Protracted infusional 5-fluorouracil (5-FU) with bolus mitomycin in 5-FU-resistant colorectal cancer.

BACKGROUND: MF (protracted infusion 5-fluorouracil (5-FU), 300 mg/m2/24 hours plus bolus mitomycin, 7 mg/m2 every 6 weeks, maximum 4 doses), was recently shown in a randomised trial to be superior to protracted 5-FU alone, as first-line chemotherapy for metastatic colorectal cancer (Ross et al. Ann Oncol 1997; 8: 995-1001 [5]). We have examined the same regimen in patients with 5-FU-resistant disease. PATIENTS AND METHODS: MF was given to 24 patients with metastatic colorectal cancer, median age 63 years. Two had progressed within four months of adjuvant 5-FU; the rest had already received palliative 5-FU, with progression during (11 patients), within four months (5 patients) or after four months of completion (6 patients). The prior 5-FU regimens were bolus 5-FU/FA (8 patients); 48 hour bolus + infusion 5-FU/FA (18 patients) or protracted 5-FU alone (3 patients). Five patients had received more than one prior 5-FU regimen. RESULTS: Three patients, 12.5%, achieved WHO partial response; seven others had minor response or stable disease (SD or better = 42%, 95% confidence interval (95% CI): 22%-64%). Median failure-free survival (FFS) was 15 weeks; median overall survival was 9.0 months. No grade 3 or 4 drug toxicity occurred, but dose reduction and/or interruption for persistent grade 2 toxicity was required in eight patients (33%). Three patients (12.5%) had venous line problems (2 thrombosis; 1 dislodged). There were no toxic deaths. 12 patients (50%) went on to receive third-line therapy after MF, including irinotecan or oxaliplatin. CONCLUSIONS: MF is a low-cost, well-tolerated regimen in second-line treatment of metastatic colorectal cancer. The response rate and FFS obtained in this small group are similar to those reported for single agent irinotecan. Half our patients obtained a useful period of control with MF before moving on to further treatment with new agents such as irinotecan and oxaliplatin.

Adult↗
PubMed2000

Cytogenetically cryptic AML1-ETO and CBF beta-MYH11 gene rearrangements: incidence in 412 cases of acute myeloid leukaemia.

The rearrangements t(8;21)(q22;22) and inv(16)(p13q22) are two of the most frequently seen in acute myeloid leukaemia (AML), accounting for 8% and 4% of cases respectively. Detection of these abnormalities is important for disease management as both are associated with good responses to conventional chemotherapy and prolonged disease-free survival. Recent reports using reverse transcriptase polymerase chain reaction (RT-PCR) suggest that significant proportions of AML cases without a visible t(8;21) or inv(16) show expression of an abnormal fusion gene transcript and, consequently, they could not be detected using conventional cytogenetic analysis alone. We present here a four centre study involving 412 cases of AML screened using both standard cytogenetics and RT-PCR for AML1-ETO and CBF beta-MYH11. We detected a cytogenetic t(8;21) in 31 out of 412 (7.5%) cases and an inv(16) or t(16;16) variant in 27 out of 412 (6.6%) cases. RT-PCR detected only two cases (0.5%) of cryptic t(8;21) and no instances of cryptic inv(16). Both cryptic t(8;21) cases had the classic M2 FAB morphology for this type of disease. Our data concur with the established FAB type distribution of the rearrangements and indicate that cryptic t(8;21) and inv(16) may be much less frequent than reported elsewhere.

Acute Disease↗
PubMed2000

Characterization of cells collected from the normal human ocular surface by contact lens cytology.

PURPOSE: In this investigation, we characterized cells collected from the normal human ocular surface using contact lens cytology (CLC). METHODS: Cells were characterized over the course of a day in three different ways. In experiment 1, we collected samples from 10 subjects six times during 1 day. Cell viability was determined by a calcein-ethidium assay. The same collection methods were used in experiment 2, but cell types were identified by fluorescent probes AE5 (corneal epithelium), AE1, AE3 (all epithelium), and T200 (all inflammatory cells). In experiment 3, cells were collected from five subjects two times in 1 day and characterized by fluorescent probes CD3 (T cells) and CD19 (B cells). For morning samples, we used an HLA-DR probe and transmission electron microscopy to examine the inflammatory activation of collected cells. RESULTS: We found viable and nonviable cells in all CLC samples, as well as an intermediate cell type that stained with both calcein and ethidium. There was a diurnal variation in cell numbers over the course of I day in viability and cell type assays, with greater cell numbers collected in the morning and evening, and fewest at midday. In the late afternoon and evening, there was an increase in corneal epithelial cell counts. There were more inflammatory cells in morning collections that included polymorphonuclear cells (PMNs). Many of these were HLA-DR+ and actively phagocytic, reflecting the immune activation of cells. CONCLUSION: The ocular surface is a dynamic environment characterized by cyclical shedding of the epithelium and active monitoring by immune cells.

Adolescent↗
PubMed2000

Regeneration of functional bladder substitutes using large segment acellular matrix allografts in a porcine model.

PURPOSE: We previously reported on the short-term (4 weeks) morphometric analysis of a large bladder acellular matrix allograft used as a bladder bioprosthesis (average size 24 cm.2). We demonstrated cellular repopulation through the entire thickness of the graft. We now present the long-term (12 weeks) morphometric results of graft regenerated porcine bladders using segments measuring an average of 40 cm.2. MATERIALS AND METHODS: Bladders harvested from pigs were subjected to detergent and enzymatic extractions to render them acellular. Partial cystectomy was performed in 21 pigs and the defect was repaired with a bladder acellular matrix allograft (average size 40.52 cm.2). Of the animals 8 were sacrificed at 1, 2 and 4 weeks and 13 were sacrificed at 8 and 12 weeks. To evaluate cellular repopulation and matrix reorganization the native bladder and graft were analyzed using standard histological and immunofluorescent techniques. To evaluate for calcium deposits in the grafts a radiological evaluation of the graft was performed after explantation. RESULTS: All animals survived the surgical procedure and there were no significant urinary leaks. No stones were noted in any of the bladders. At 1 week there was a diffuse infiltration with acute inflammatory cells. At 2 weeks the luminal surface of the graft was lined with a single layer of urothelium, and there was stromal infiltration with unorganized smooth muscle cells and angiogenesis. At 4 weeks the urothelium was multilayered with organizing groups of smooth muscle cells and angiogenesis. At 8 and 12 weeks there was repopulation throughout the bladder acellular matrix allograft implant with all native cellular components participating. CONCLUSIONS: We present evidence that large patch bladder acellular matrix allograft implantation is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. Its advantages may include the potential for complete and functional regeneration of a bladder substitute.

Animals↗
PubMed2000

Enhancement of A spermatogonial proliferation and differentiation in irradiated rats by gonadotropin-releasing hormone antagonist administration.

The initial changes in the numbers, proliferation, and differentiation of A spermatogonia in irradiated rats after the administration of a GnRH antagonist, which is known to induce differentiation in this system, were investigated. LBNF1 rats were given 6 Gy of gamma-irradiation; some were treated with the GnRH antagonist Cetrorelix beginning 15 weeks after irradiation. Although the spermatogonia in the irradiated rats without hormone treatment continue to proliferate (labeling and mitotic indexes of 24% and 18%, respectively), they underwent apoptosis (apoptotic indexes of 21% by the terminal transferase-mediated end labeling assay and 9% by nuclear morphology), resulting in a constant number of A spermatogonia. Whole mount analysis of clones ofA spermatogonia revealed that larger clones were more likely to undergo apoptosis than mitosis. Hormone administration decreased the intratesticular testosterone concentration to 6% of the level in irradiated rats within 1 week. Concomitantly, there was a decrease in spermatogonial apoptotic indexes to 43% of levels in irradiated-only rats, leading to an increases in their numbers by 150%, their diameters by 11%, and their labeling indexes by 31%. The sizes of the mitotic clones gradually increased, and clones of more than eight cells appeared at week 3 of hormone treatment. A spermatogonial differentiation began at week 4, and by week 6.6, differentiation occurred in 30% of the tubules. Thus, suppression of intratesticular testosterone by the GnRH antagonist may be responsible for the immediate changes in spermatogonial numbers and kinetics, but several additional steps are required before differentiation begins, which did not occur until week 4.

Animals↗
PubMed2000

Gonadotropin-releasing hormone analogs stimulate and testosterone inhibits the recovery of spermatogenesis in irradiated rats.

We investigated the effects of GnRH analogs, different doses of testosterone (T), an androgen receptor antagonist (flutamide), and combinations of these on the recovery of spermatogenesis after irradiation. Treatment with a GnRH agonist (Lupron) for 10 weeks after irradiation reduced the intratesticular T concentration (ITT) to 4% of that in irradiated rats and serum FSH to undetectable levels without altering serum LH levels. Injection of a GnRH antagonist (Cetrorelix) at 3 weeks after irradiation suppressed LH, FSH, and ITT to <7%, 32%, and 10%, respectively, of levels in irradiated-only rats within 2 weeks; suppression was maintained for approximately 3 to 4 weeks. The percentage of tubules with differentiated germ cells (repopulation index, RI) was <0.6% at weeks 10 to 20 after irradiation. Spermatogenic recovery was induced by both the GnRH agonist (RI = 58% at week 10; 91% at week 20) and antagonist (RI = 70% at week 13). There was a dose-dependent suppression of testicular germ cell repopulation when T was combined with GnRH analogs. The ability of T to abolish the spermatogenic stimulatory effect of the GnRH antagonist was evident by the similar RI obtained for irradiated rats given antagonist + T or T alone. This suppression of GnRH-induced recovery of spermatogenesis by T could be reversed by flutamide. The RI best correlated with the degree of ITT suppression. In ITT-suppressed rats, the RI also showed an inverse correlation with serum T levels. Thus, T and/or its androgenic metabolites either directly or indirectly inhibit spermatogenic recovery after irradiation through an androgen receptor-mediated process. In addition, there was a close negative correlation between RI and FSH levels, and hence, a spermatogenic inhibitory role for FSH in the irradiated rats cannot be ruled out.

Androgen Antagonists↗
PubMed2000

Pulmonary cyst and cerebral arterial gas embolism in a hypobaric chamber: a case report.

This is a report of an aircrew member who suffered a serious physiological incident in the form of pulmonary barotrauma and cerebral arterial gas embolism during hypobaric chamber training, and who subsequently was shown to have a cyst in the upper lobe of the left lung. The likely origin of the cyst is discussed, as well as the aeromedical disposition following thoracotomy and apical segmentectomy to remove the cyst.

Adult↗
PubMed2000

Apoptosis in shed human corneal cells.

PURPOSE: To determine whether shear forces applied to the corneal epithelium by the repeated insertion and removal of a hydrogel contact lens alter the size and number of cells removed and to determine the contribution of apoptosis to this process. METHODS; Human corneal cells were collected from eight healthy subjects by sequential contact lens cytology (20 lens insertions and removals). Collected cells were stained with acridine orange for counting and measurement of cell size. In a separate experiment, collected cells were fixed and stained with TdT-mediated dUTP nick-end labeling (TUNEL) or labeled immediately after collection using annexin V. Hoechst stain and propidium iodide (PI) were used as nuclear counterstains. The proportion of cells labeled with acridine orange, TUNEL, and annexin V was quantified by fluorescence microscopy. RESULTS; The number of cells increased in later collections, and cells were smaller. The mean number of positively stained cells using TUNEL was 57%. Annexin V labeling on unfixed fresh samples showed a mean of 64%, with an increase in later collections. Apoptotic bodies were observed in very few cells. In most cells the nucleus and cytoplasmic membrane were intact. Structures were observed in which nuclei were missing (Hoechst negative) but in which cytoplasm had the size and appearance of whole, nucleated cells. These structures (cell ghosts) increased in number along with the increase in nucleated cells in later collections. CONCLUSIONS: The sequential removal of a soft contact lens caused a progressive increase in the number of cells collected from the surface and a progressive decrease in their size. The majority of nucleated cells removed by a contact lens were apoptotic in the sense of being positively labeled by TUNEL and annexin V. Morphologically they differed from classically apoptotic cells, in that cells showed an intact nuclear structure and no discernible apoptotic bodies. They could represent a last stage in a pathway of cell differentiation in which frictional forces induced by the removal of the contact lens activate the apoptotic program and cause the cell to be shed. There is also a pathway in which cells lose their nuclei before leaving the epithelial surface.

Acridine Orange↗
PubMed2000

Further analysis of the size and shape of cells obtained by impression cytology from the exposed portion of the human bulbar conjunctiva.

PURPOSE: To assess whether the size of the cells obtained by conjunctival impression cytology can be quantitatively assessed by measurement of the longest dimension of the cells. METHODS: Under topical benoxinate anaesthesia, cells were removed from the normally exposed nasal bulbar conjunctival surface using a 0.4 micron pore diameter filter (Biopore filter; type Millcell-CM). The filters were stained with haematoxylin after ethanol denaturation, photographed at 40 x magnification, and 35 mm slides prepared. An optical overlay method was used to outline the borders of sets of 30-35 contiguous cells on each image. The cell area, longest and shortest dimensions were measured by planimetry to an accuracy of +/- 3%. RESULTS: Analyses of 20 sets of samples, from individuals aged 21 to 48 years and without clinically significant ocular surface disease, revealed a median cell area of 133 micron 2 (n = 621, range 46-1602 micron 2; average 212 micron 2), a median longest dimension of 13.9 microns (range 6.6-68.8 microns; average 16.9 microns) and a shorter dimension of 10.0 microns (range 4.7-43.0 microns; average 11.9 microns); the distributions of values indicated bimodality. Most cells had a long:short ratio (L:S ratio) value between 1.00 and 1.80, but 11.9 +/- 6.1% of the cells had L:S ratios between 1.80 and 4.60. The overall relationship between the longest dimension and the area of the cells was nonlinear, with cells having larger L:S ratios having disproportionately smaller areas. CONCLUSIONS: The superficial conjunctival cells are small, and their longest dimensions are systematically related to area. Analyses of cell shape indicate further possible ways of identifying different cells on the bulbar conjunctiva. Compared to literature values, there is a substantial overlap in longest dimensions of the conjunctival cells with those of cells that can be collected off the corneal surface. This means that superficial conjunctival and corneal cells cannot be distinguished simply on the basis of measurements of the long dimension.

Adult↗
PubMed2000

In vivo targeting of malignant melanoma by 125Iodine- and 99mTechnetium-labeled single-chain Fv fragments against high molecular weight melanoma-associated antigen.

Monoclonal antibodies (MAbs) against high-molecular-weight melanoma-associated antigen (HMW-MAA) have been used in vivo to target melanoma. More recently, single chain Fv (scFv) antibody fragments against HMW-MAA have been described that may improve melanoma targeting. However, there have been few in vivo studies with antimelanoma scFvs because these have proved difficult to label with isotopes (e.g., 99mTc) suitable for imaging. We have generated a series of scFvs against HMW-MAA by chain shuffling and antibody phage selection on melanoma cells. In preliminary experiments we identified one scFv (RAFT3) as suitable for in vivo melanoma targeting. Direct radiolabeling of RAFT3 scFv with 99mTc was simple, yielding a radiochemical purity of >90%. The label remained stable for 24 h in vitro. 125I- and 99mTc-labeled RAFT3 scFv were tested in a nude mouse xenograft model for human melanoma and were compared with the parent MAb LHM2 and its F(ab')2 fragment versus nonmelanoma-specific MAb and scFv. RAFT3 scFv accumulated specifically in the tumor and showed greater tumor specificity compared with LHM2 with faster pharmacokinetics (t(1/2)alpha, 8 min; t(1/2)beta, 189 min; and t(1/2)alpha, 37 min; t(1/2)beta, 384 min, respectively) and reduced background in liver, lung, and spleen. Nonspecific accumulation of 99mTc-labeled RAFT3 scFv in the kidney was high but tumor:normal tissue ratios were better compared with 125I-labeled RAFT3 scFv and LHM2 F(ab')2. Overall, tumor-targeting efficiency at equivalent time points was scFv > IgG > F(ab')2 in good agreement with previously described scFvs engineered for 99mTc labeling. We discuss the potential use of RAFT3 scFv for imaging and therapy of metastatic melanoma.

Animals↗