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Biomedical subjects

B J Smith

Publications and source records attributed to B J Smith.

At least 127 records · Page 7Linked to original sources
PubMed1997

Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma.

OBJECTIVES: To determine the efficacy and dose response of subconjunctival carboplatin with and without cryotherapy in the treatment of murine transgenic hereditary retinoblastoma. METHODS: Fifty-one 5-week-old transgenic BLH SV-40 (Charles Rivers Laboratories, Boston, Mass) T-antigen-positive mice with retinoblastoma were administered 6 subconjunctival injections of carboplatin in 1 eye at drug doses of 10, 15, 20, 25, 62.5, 125, and 250 microg. Six control eyes received 6 subconjunctival injections of balanced salt solution. Fourteen of the 51 subconjunctivally treated eyes received a single application of transconjunctival cryotherapy immediately prior to each carboplatin injection. Six control eyes received 6 single applications of transconjunctival cryotherapy using the above schedule but did not receive carboplatin. All experimental and control eyes were obtained at 16 weeks of age for histopathologic examination. RESULTS: A dose-dependent inhibition of intraocular tumor growth by subconjunctivally delivered carboplatin was observed in these transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 180 microg. In animals treated with cryotherapy alone, no tumor control was noted (0 of 6). In animals treated with subconjunctival carboplatin coupled with cryotherapy, a tumor control dose of 417 microg was found. No evidence of histopathologic treatment toxicity was noted. CONCLUSIONS: Subconjunctival delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent fashion in a transgenic murine retinoblastoma model. Cryotherapy does not increase tumor control in this murine retinoblastoma model.

Animals↗
PubMed1997

Evidence that initiated keratinocytes clonally expand into multiple existing hair follicles during papilloma histogenesis in SENCAR mouse skin.

We have previously shown that the precursors of cutaneous papillomas in SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate are focal hyperplastic lesions that we refer to as squamous cell hyperplastic foci (SCHF). Ha-ras gene codon 61 mutations were frequently found in SCHF, providing evidence that these lesions represent clones of initiated cells. We report here the pathogenesis of multiple hair follicle involvement in more advanced SCHF and describe the role of the hair follicle in papilloma histogenesis. Detailed histological evaluation of 83 SCHF and 25 early papillomas revealed a morphological continuum from the least developed SCHF, involving only one hair follicle, to advanced SCHF and early papillomas, which involved more than 10 hair follicles. These results provide evidence of the recruitment of additional hair follicles as SCHF progress. In advanced SCHF and early papillomas the bulk of the epithelial component in all cases consisted of several markedly hyperplastic adjacent hair follicles, whereas the involved interfollicular epidermis (IFE) was generally less hyperplastic. All of the hair follicles involved in SCHF appeared to have been preexisting, based on their pattern of spacing, that they were consistently normal appearing below the level of the sebaceous glands, and that they were in the same phase of the hair cycle as surrounding, uninvolved hair follicles. Also, no evidence of follicular neogenesis was observed in serially sectioned SCHF, and coalescence of smaller lesions was rare. To investigate whether the involvement of multiple hair follicles in SCHF was due to expansion of initiated cells into existing hair follicles or, possibly, to a paracrine mechanism, we analyzed different levels of three serially sectioned SCHF and one early papilloma for Ha-ras mutations. These analyses revealed cells with Ha-ras gene codon 61 mutations at multiple levels that involved different hair follicles. Overall, our results provide evidence that as initiated cells clonally expand, they spread across the IFE and populate the upper permanent portions of existing hair follicles. The abnormal proliferation of the infundibula of the hair follicles involved in SCHF appears to give rise to most of the epithelial component of papillomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Hippocampal connexin 43 expression in human complex partial seizure disorder.

An increase in the cellular production of gap junction proteins and increased numbers of gap junctions in the neuronoglial syncytium of an epileptic focus have been proposed as a possible mechanism underlying synchronization of discharge. To study this issue, both Northern and Western blot analyses of the gap junction protein connexin 43 mRNA and protein abundance were performed on hippocampal tissue resected from patients presenting with a complex partial seizure disorder arising from the medial temporal area and the hippocampus in particular. Samples from 15 patients with medically intractable seizures were compared to those from 5 nonepileptic patients requiring temporal lobectomy in life-threatening situations. Six of the 15 epileptic patients underwent noninvasive electrographic recording, whereas the remaining 9 patients required intracerebral electrodes for extraoperative recording and therefore showed a more discrete focality than the noninvasive recordings. A decline in the mean levels of connexin 43 mRNA expressed predominantly in astrocytes was noted in the epileptic patient groups, particularly for those cases requiring intracranial electrode placement where ictal onset was more clearly established to be intrahippocampal. Quantitation of connexin 43 protein in both epileptogenic and nonepileptogenic hippocampal tissues showed no significant differences in expression. Although mean values for mRNA showed a decline, clinical outcomes postoperatively showed no correlation with either mRNA or protein expression individually in our epileptic population. The findings indicate that there is effectively no upregulation of mRNA and no increased production of connexin 43 protein in response to the development of epileptogenicity. Rather it appears the influence of gap junctions as a substrate of epileptogenicity in any mechanism(s) underlying synchrony or electrical propagation may be a function of the dynamic state (open versus closed) of the membrane-bound gap junction.

Adult↗
PubMed1997

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures.

Humans were trained to discriminate the benzodiazepine triazolam (0.32 mg/70 kg) from placebo under a two-response (drug vs. placebo) drug discrimination procedure. Dose-effect curves for several drugs were then determined in a crossover design using the two-response procedure and a 'novel-response procedure' that provided a novel-appropriate response for drugs unlike triazolam or placebo. Three subjects were tested with triazolam (0.1-0.32 mg/70 kg), the barbiturate secobarbital (56-177 mg/70 kg), and caffeine (320 and 560 mg/70 kg). Triazolam dose dependently increased triazolam-appropriate responding under both procedures and generally did not occasion novel-appropriate responding under the novel-response procedure. Secobarbital substituted for triazolam in the two-response procedure and dose-dependently increased novel-appropriate responding as well as occasioned some triazolam-appropriate responding in the novel-response procedure. Caffeine generally occasioned placebo-appropriate responding under the two-response procedure and a mix of novel- and placebo-appropriate responding under the novel-response procedure. Triazolam and secobarbital produced qualitatively similar self-reported drug effects. These results suggest that the novel-response procedure for human drug discrimination may enhance the pharmacological selectivity of triazolam- and placebo-appropriate responding.

Adult↗
PubMed1997

A prospective study of Astra single tooth implants.

A new design of single tooth implant (AstraTech, Molndal Sweden) featuring a microthreaded conical neck and TiO blast surface was evaluated clinically and radiographically after 2 years in function. Fifteen patients (age range 16 to 48) with missing maxillary anterior teeth (6 central incisors, 8 laterals, 1 bicuspid) had 4, 13 mm and 11, 15 mm implants placed under local anaesthesia and left for a period of 6 months before exposure and abutment connection/crown fabrication. All patients were seen at 4 to 6 monthly intervals for hygienist maintenance. Radiographs using Rinn holders and a long cone technique were taken at the crown insertion and after 1 year (14 subjects) and 2 years (12 subjects). All implants were successfully integrated at stage 2, and no implants have been lost. The internal conical seal design of the abutment/implant interface facilitated connection and there were no cases of abutment screw loosening. No soft tissue problems were observed, and the gingival morphology/health was well maintained. One crown was recemented after 18 months in function, and 1 crown was replaced because of a fracture to the porcelain incisal edge. At crown insertion, the mean bone level was 0.46 to 0.48 mm apical to the top of the implant and there were no statistically significant changes in the bone level over the 2 years of the study. In conclusion, the single tooth Astra implants were highly successful and bone changes within the first 2 years of function were comparable with other systems reporting high long-term success rates.

Adolescent↗
PubMed1997

Corneal responses to lens transmissibility.

BACKGROUND: Lens transmissibility (Dk/L) and corneal relief from hypoxia are not linearly related. We describe graphically and by equations the relationship between corneal relief (scaled in oxygen shortfall units) and Dk/L across the transmissibility range of 1.2 to 189 x 10(-9) (cm/sec)(ml O2/ml mmHg). METHODS: Corneal responses to 28 Dk/L levels across the transmissibility range were expressed in oxygen shortfall units (osús), a relative scale of 100 steps bounded by each cornea's normal oxygen uptake rate with no contact lens in place (set = to 0 osús), and its maximum uptake rate for the open eye due to static PMMA lens wear (set = to 100), thus allowing the degree of hypoxic stress exhibited by all corneas to be compared on the same relative scale. RESULTS: Responses of 11 human corneas to each of those 28 Dk/L steps were recorded across that entire transmissibility range, and their collective relationship described graphically. CONCLUSION: The graphic composite of all corneal responses to transmissibility steps across the Dk/L range of 1.2 to 189 X 10(-9) (cm/sec)(ml O2/ml mmHg) was found to be monotonic and continuous. While no single equation was found that optimally described (predicted) corneal responses across that entire spectrum, equations of the quadratic form fit limited domains of Dk/L (r2 values exceeding 90%) adequately for most laboratory and clinical applications.

Adult↗
PubMed1997

A review of localized tomography.

Localized computed tomography is the field of reconstructing an image of a portion of the internal structure of an object from an incomplete set of projections. Standard computed tomographic techniques require a full set of projections even when only a small portion of the object is of interest. The first localized tomographic technique was developed in the field of non-destructive testing in 1981 by Soviet scientists. Since this initial work numerous other researchers have advanced the field of localized tomography in theoretical and applied areas. This paper reviews the diverse localized computed tomography field.

Image Processing, Computer-Assisted↗
PubMed1996

Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.

Animals↗
PubMed1996

Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor-associated mortality, while maintaining excellent tumor control rates. OBJECTIVE: To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma. METHODS: Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 micrograms) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma. RESULTS: No eye treated with 0.1 microgram of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 microgram of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 microgram of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 micrograms of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24. CONCLUSIONS: Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy.

Animals↗
PubMed1996

Fine structure of the retinal pigment epithelium of the barred owl (Strix varia).

The retinal pigment epithelium (RPE) as well as the choriocapillaris and Bruch's membrane (complexus basalis) have been studied by light and electron microscopy in the barred owl (Strix varia). The RPE consists of a single layer of cuboidal cells joined laterally by a series of tight junctions that forms part of the blood-ocular barrier. Basally (sclerally) the retinal epithelial cells display numerous deep infoldings while apically (vitreally) microvillar processes interdigitate with the photoreceptor outer segments. Internally the RPE cells show a large vesicular nucleus, plentiful smooth endoplasmic reticulum (SER) and polysomes but very little rough endoplasmic reticulum (RER). Numerous pleomorphic (including ring-shaped) mitochondria are basally located. In the light-adapted state the small melanosomes are almost exclusively located within the apical process indicating that retinomotor movements probably occur. Phagosomes and lysosome-like bodies are present as are myeloid bodies which may show ribosomes on their outer surface. Bruch's membrane is typical of avian species in that it is pentalaminate and the central lamina densa is displaced towards the choroid. The choriocapillaris endothelium is thin but only minimally fenestrated facing Bruch's membrane. Most fenestrations present show a single-layered diaphragm while others display a double-layered diaphragm as noted in other avian species.

Animals↗
PubMed1996

Fine structure of the retinal photoreceptors of the barred owl (Strix varia).

The photoreceptors of the barred owl (Strix varia) consist of rods, single cones and unequal double cones present in a ratio of about 35:1:3. In the light-adapted condition the rods are of uniform diameter along their entire length and are therefore not felt to undergo photomechanical changes. The rod outer segment consists of a stack of scalloped bimembranous discs enclosed in a limiting membrane. The rod inner segment displays an ellipsoid of mitochondria, much rough endoplasmic reticulum (RER), numerous polysomes, Golgi zones and autophagic vacuoles, but no hyperboloid of glycogen. Single cones show a slightly tapered outer segment and a heterogeneous oil droplet along with an ellipsoid of mitochondria at the apex of the inner segment. Double cones consist of a larger chief member which also displays a heterogeneous oil droplet and a slightly smaller accessory member which does not. Both members of the double cone as well as the single cones show plentiful polysomes and RER as well as Golgi zones in the inner segment, but none of the cones possessed a condensed paraboloid of glycogen. The contiguous membranes of the chief and accessory cones displayed a few presumed junctional complexes. Judging by their elongated shape in the light-adapted state, cones in this species do not undergo retinomotor movements. Rods and both types of cones have both invaginated (ribbon) and superficial (conventional) synaptic sites.

Animals↗