Characterization of high-affinity receptors for bombesin/gastrin releasing peptide on the human prostate cancer cell lines PC-3 and DU-145: Internalization of receptor bound 125I-(Tyr4) bombesin by tumor cells

Specific receptors for bombesin/gastrin releasing peptide (GRP) on the androgen-independent human prostate cancer cell lines PC-3 and DU-145 were characterized. No specific binding of ¹²⁵I-[Tyr⁴]-bombesin to the androgen-dependent human prostate cancer cell line LNCaP was detectable. The binding of ¹²⁵I-[Tyr⁴]-bombesin to PC-3 and DU-145 cells was found to be time- and temperature-dependent, saturable, and reversible. Scatchard analysis revealed a single class of binding sites with high affinity (K_d 9.8 × 10^?11 M for PC-3, and 9.1 × 10-¹¹ M for DU-145 cells at 25°C) and with a binding capacity of 44,000 binding sites/cell and 19,000 binding sites/cell, respectively. Bound ¹²⁵I-[Tyr⁴]-bombesin was rapidly internalized by PC-3 cells. The nonhydrolyzable GTP analog GTP-gamma-S caused a dose-dependent inhibition of ¹²⁵I-[Tyr⁴]-bombesin binding to PC-3 and DU-145 cells, indicating that a G-protein (guanine nucleotide-binding protein) couples the bombesin receptor to intracellular effector systems. Bombesin and GRP(14-27) inhibited the binding of ¹²⁵I-[Tyr⁴]-bombesin to both cell lines in a dose-dependent manner with inhibition constants (K_i of 0.5 nM and 0.4 nM, respectively. Both cell lines express the bombesin/GRP preferring bombesin receptor subtype, since, in displacement studies, neuromedin B was more than 200 times less potent than bombesin and GRP(14-27) in inhibiting the binding of ¹²⁵I-[Tyr⁴]-bombesin. Two synthetic bombesin/GRP antagonists, RC-3095 and RC-3110, powerfully inhibited the specific binding of ¹²⁵I-[Tyr⁴]-bombesin with K_i 0.92 nM and 0.26 nM on PC-3 cells, and 3.3 nM and 0.89 nM on DU-145 cells, respectively. These findings indicate that the PC-3 and DU-145 human prostate cancer cell lines possess specific high-affinity receptors for bombesin/GRP, and are suitable models for the evaluation of the antineoplastic activity of new bombesin/GRP antagonists in the treatment of androgen-independent prostate cancer. © 1994 Wiley-Liss, Inc.     

Synaptogenesis in the Prefrontal Cortex of Rhesus Monkeys

Since the turn of the century, the prefrontal association areasof the cerebral cortex have been thought to be among the lastregions of the cortical mantle to develop. We have examinedthe course of synaptogenesis in the macaque prefrontal cortexby quantitative electron microscopic analysis in 25 rhesus monkeysranging in age from embryonic day 47 (E47) to 20 years of age.A series of overlapping electron micrographs spanning the wholecortical thickness in each animal provided data on the number,the proportion, and the density of synapses per unit area (N_A)and per unit volume (N_V) of neuropil. The tempo and kinetics of synapse formation in prefrontal cortexclosely resemble those described for sensory and motor areas,particularly during the stages of synapse acquisition and overproduction(Rakic et al., 1986). In young embryos, we describe a precorticalphase (E47-E78), when synapses are found only above and below,but not within, the cortical plate. Following that, there isan early cortical phase, from E78 to E104, during which synapsesaccumulate within the cortical plate, initially exclusivelyon dendritic shafts. The next rapid phase of synaptogenesisbegins at 2 months before birth and ends approximately at 2months after birth, culminating with a mean density of 750 millionsynapses per cubic micrometer. This accumulation is largelyaccounted for by a selective increase in axospine synapses inthe supragranular layers. The period of explosive synaptic densityis followed by a protracted plateau stage that lasts from 2months to 3 years of age when synaptic density remains relativelyconstant. The final period of decline, from 3 years throughover 20 years of age, is marked by a slight but statisticallysignificant decline in synaptic density. Concurrent recruitment of synapses with that of sensory andmotor areas supports the concept that the initial establishmentof cortical circuitry is governed by general mechanisms commonto all areas, independent of their specific functional domain.The finding that synaptic density is relatively stable fromearly adolescence through puberty (the plateau period) is indicativeof the importance, in primates, of a consistent and high synapticdensity during the formative years when learning experiencesare most intense.     

FASCIOCUTANEOUS ISLAND FLAPS FOR ORTHOPAEDIC MANAGEMENT IN LOWER LIMB RECONSTRUCTION USING DERMATOMAL PRECINCTS

This paper describes a technique of fasciocutaneous island flaps used in reconstruction of the lower limb. It is very versatile and some 26 individual flaps in 22 patients have been used to reconstruct skeletal and soft tissue problems from the popliteal fossa to the ankle joint. These longitudinally designed flaps made up of a trilaminate of skin, subcutaneous fat and fascia are aligned within the dermatomal precincts. The most important location for such flap design is along the peroneal compartment sitting within the L5 dermatome and incorporating the superficial peroneal nerve. It can be lengthened as far as the lateral malleolus and is an excellent reconstructive method to close defects over the lower third of the tibia. The medial compartment of the leg employing the saphenous nerve (L4 dermatome) is another area for fasciocutaneous island flap reconstruction, but use is restricted to the upper two-thirds of the tibial area. Posteriorly the island flap design sits along the S2 dermatome, this time incorporating the sural nerve to reconstruct defects of the calf and can be extended to include problems of the popliteal fossa. In the overall flap technique, the age of the patient is not a contraindication and cases with peripheral vascular disease have been treated successfully. The flaps may extend up to a 5:1 ratio in dimension. The operating time can be considerably shortened.     

Dronabinol reduces signs and symptoms of idiopathic intracranial hypertension: a case report.

A case is presented in which a woman diagnosed with a longstanding history of idiopathic intracranial hypertension reported improvement of frontal headaches, photophobia, transient blindness, enlarged blind spots, and tinnitus after smoking marijuana. All these symptoms and signs were associated with increased intracranial pressure (220-425 mm of water). Treatment with dronabinol at a dose of 10 mg twice a day, then reduced to 5 mg twice a day, relieved all of her symptoms. Previously noted papilledema and enlargement of blind spots also resolved, and this, in the absence of psychoactive effect or weight gain.     

Spectral characteristics of speech at the ear: implications for amplification in children.

This study examined the long- and short-term spectral characteristics of speech simultaneously recorded at the ear and at a reference microphone position (30 cm at 0 degrees azimuth). Twenty adults and 26 children (2-4 years of age) with normal hearing were asked to produce 9 short sentences in a quiet environment. Long-term average speech spectra (LTASS) were calculated for the concatenated sentences, and short-term spectra were calculated for selected phonemes within the sentences (/m/, /n/, /s/, [see text], /f/, /a/, /u/, and /i/). Relative to the reference microphone position, the LTASS at the ear showed higher amplitudes for frequencies below 1 kHz and lower amplitudes for frequencies above 2 kHz for both groups. At both microphone positions, the short-term spectra of the children's phonemes revealed reduced amplitudes for /s/ and [see text] and for vowel energy above 2 kHz relative to the adults' phonemes. The results of this study suggest that, for listeners with hearing loss (a) the talker's own voice through a hearing instrument would contain lower overall energy at frequencies above 2 kHz relative to speech originating in front of the talker, (b) a child's own speech would contain even lower energy above 2 kHz because of adult-child differences in overall amplitude, and (c) frequency regions important to normal speech development (e.g., high-frequency energy in the phonemes /s/ and [see text]) may not be amplified sufficiently by many hearing instruments.     

Work life of persons with asthma, rhinitis, and COPD: A study using a national, population-based sample

Objective  

To estimate the duration of work life among persons reporting a physician's diagnosis of COPD, asthma, or rhinitis compared to those with select non-respiratory conditions or none and to delineate the factors associated with continuance of employment.     

Improved documentation of wound care with a structured encounter form in the pediatric emergency department.

OBJECTIVE: Accurate and complete documentation may enhance reimbursement and compliance with financial intermediary regulations, protect against litigation, and improve patient care. We measured the effect of introduction of a structured encounter form on the completeness of documentation of pediatric wound management in a teaching hospital. METHODS: The Children's Hospital Emergency Department introduced a structured encounter form for use in the documentation of wound care in place of the existing free-text dictation method. Attending physicians and trainees, all unaware of the study, had the option of using the form in place of free-text dictation for patients with lacerations requiring closure. We abstracted 100 consecutive free-text dictations from patients treated before the form's introduction. Following a 3-month run-in period, we abstracted 100 consecutive structured wound records. We compared the 2 chart types for completeness of documentation based on 20 predetermined criteria relevant to pediatric wound care. RESULTS: Overall completeness of documentation improved with structured forms (80% vs 68% for free text, P < .001), with significant improvements in 6 of 20 individual criteria. Trainees demonstrated improvement in documentation with the structured form, with the greatest improvements among senior-level residents. Documentation of the general physical examination worsened with structured charting. DISCUSSION: In an academic pediatric emergency department, the use of a structured complaint-specific form improved overall completeness of wound-care documentation. Structured encounter forms may provide for more standardized documentation for a variety of pediatric chief complaints, thereby facilitating communication and ultimately transition to template-driven systems in anticipation of an electronic medical record.