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We studied the ligand-induced endocytosis of the yeast alpha-factor receptor Ste2p by immuno-electron microscopy. We observed and quantitated time-dependent loss of Ste2p from the plasma membrane of cells exposed to alpha-factor. This ligand-induced internalization of Ste2p was blocked in the well-characterized endocytosis-deficient mutant sac6Delta. We provide evidence that implicates furrow-like invaginations of the plasma membrane as the site of receptor internalization. These invaginations are distinct from the finger-like plasma membrane invaginations within actin cortical patches. Consistent with this, we show that Ste2p is not located within the cortical actin patch before and during receptor-mediated endocytosis. In wild-type cells exposed to alpha-factor we also observed and quantitated a time-dependent accumulation of Ste2p in intracellular, membrane-bound compartments. These compartments have a characteristic electron density but variable shape and size and are often located adjacent to the vacuole. In immuno-electron microscopy experiments these compartments labeled with antibodies directed against the rab5 homologue Ypt51p (Vps21p), the resident vacuolar protease carboxypeptidase Y, and the vacuolar H+-ATPase Vph1p. Using a new double-labeling technique we have colocalized antibodies against Ste2p and carboxypeptidase Y to this compartment, thereby identifying these compartments as prevacuolar late endosomes.

The three-dimensional guidance system for implant insertion is a technique for placing a radiopaque vertical orientation pin over the crest of the alveolar ridge on the stone cast during fabrication of the radiographic guide. The cross-sectional and panoramic reformatted images were reproduced on a Polaroid or 35-mm print. The true vertical orientation pin facilitates (1) identification and the exact planned location of each implant in the reformatted images of the CT scan, (2) establishment of the internal starting point for the osteotomy on a photographic print, (3) optimum implant orientation, and (4) measurement of the angulation between the true vertical orientation line and optimum implant orientation. With the aid of a newly developed dual-axes base and transfer of the internal starting point of each implant to the stone cast, the buccolingual and mesiodistal implant inclinations for each implant were transferred to a surgical guide in the form of surgical steel drill guide tubes. The resulting pilot osteotomy transfers to the alveolar bone the exact starting point and the buccolingual and mesiodistal inclination for each implant. The technique provides a three-dimensional guidance system for implant insertion that is extremely accurate and yet practical.

A technique is presented, with two sets of newly designed drills, that facilitates three-dimensional guided insertion of implants. A radiographic guide has been fabricated with titanium markers that are transferred into the CT scan reformatted images. The resulting cross-sectional and panoramic reformatted images provide the precise location for each implant. The buccolingual and mesiodistal inclinations of each implant are measured and transferred to a surgical guide that contains steel drill guide tubes. The starting point and three-dimensional orientation of each implant is then transferred to a pilot osteotomy. The widening of an osteotomy, with end-cutting drills of the usual design, can lead to the loss of orientation because a wider drill cannot be effectively guided by a smaller diameter osteotomy. A newly designed set of drills has been developed that maintains tracking of the original orientation as the incremental increase in width proceeds. The three-dimensional guidance system for implant insertion was first accomplished in vitro and then on patients.

The supposition that staggered buccal and lingual implant offset is biomechanically advantageous was examined mathematically. The method of evaluation utilized a standard hypothetical geometric configuration from which implants could be staggered buccally and/or lingually in both arches. Torque (moment) values were calculated at the gold screw, abutment screw, and 3.5 mm apical to the head of the implant. Comparisons were made in percentages of change from the hypothetical standard to the buccal and/or lingual implant offset. In the maxillary arch, buccal offset decreased the torque (moment) while lingual offset increased it. If more lingually offset implants were present in the maxillary restoration, the total torque would be greater than if they were all in a straight line. Staggered buccolingual implant alignment often requires abutment reangulation. The resultant line of force produced by occlusal anatomy usually results in buccal inclination in the maxillary arch and lingual inclination in the mandibular arch. As a result, mandibular implant/prostheses are greatly favored over similar maxillary configurations because the mandibular resultant line of force usually passes lingually, closer to the components and supporting bone and considerably less torque is produced. Therefore, the concept of staggered offset for multiple implant-supported prostheses can be utilized on the mandible but is not recommended for the maxilla where maximum uniform buccal implant orientation is advised.

A comparative evaluation of torque at the gold screw, abutment screw, and implant was calculated for cuspal inclination, implant inclination, and horizontal and vertical implant offset. The method of comparison was expressed as a percentage of change from a hypothetical standard maxillary implant/prosthesis configuration. These data facilitate rational clinical conclusions that cuspal inclination produces the most torque, followed by maxillary horizontal implant offset, while implant inclination and apical implant offset produce minimal torque. Although these data are not intended as a quantitative analysis, they nonetheless provide a practical guide to diagnosis and treatment planning.

The force distribution of multiple tooth-supported and implant-supported prostheses is completely different. A direct correlation exists between the degree of flexion at the site of loading and the amount of force distribution to other members of the prosthesis. Micromovement produced by the periodontal fibers facilitates force distribution to all the root surfaces of the natural tooth abutments. The rigidity of the implant/abutment/prosthesis configuration concentrates the force at the crestal bone at the site of loading with limited distribution to the remaining implants. Differential mobility concentrates the force distribution to the bone support of the most rigid members of splinted natural teeth or to the implants when they are united with natural teeth in a combined prosthesis. Implants always support the natural teeth and never the other way around. Therefore a nonrigid attachment is recommended between a tooth-supported prosthesis and an implant-supported prosthesis when they are combined. However, when implants are interspersed with natural teeth in the same prosthesis, the restoration will be implant borne. This requires special force distribution analysis to prevent implant overload.

23 patients were operated on between 3 and 24 hours (group 1) and between 2 and 14 days (group 2) after a stroke with a diagnosis of carotid obstruction. A retrospective study for patients of stage IIIa and IIIb showed that clinical and functional results of both groups correspond. The mortality of group 1 was slightly less than that of group 2. Group 1 showed the largest number of successful vascular reconstructions. Thus an early operation of stage IIIa and possibly IIIb seems indicated. In view of the high mortality (5 out of 6 patients) surgery cannot be recommended in stage IV.

EDTA-soluble material, extracted from incisor teeth of rats given 50 ppm fluoride (NaF) in drinking water ad libitum from conception to age nine wk, contained significantly higher levels of protein (P less than 0.01) and gamma-carboxyglutamic acid (P less than 0.01) than did similar material from control rats. Tooth fluoride levels indicated that the incisors were mildly fluorosed. Analysis of these data indicates that mild fluorosis of rat incisor teeth involves not only the characteristic disturbances of pigmentation and mineral structure but also some alteration of the matrix protein.

Immunocytochemical techniques using monoclonal antibodies directed against T-lymphocyte surface antigens (OKT3, OKT4, and OKT8) were used to investigate changes in the T-cell subpopulations throughout the natural time course of recurrent aphthous stomatitis (RAS). All lesions contained large numbers of OKT3-positive T cells. Preulcerative lesions were characterized by many OKT4-positive inducer/helper cells and few OKT8-positive suppressor/cytotoxic cells (T4:T8 approximately equal to 2:1). The ulcerative lesion contained large numbers of OKT8-positive suppressor/cytotoxic cells and only a very small number of OKT4-positive cells (T4:T8 approximately equal to 1:10). The healing lesion once again became dominated by OKT4-positive cells, with only a small number of OKT8 positive cells present (T4:T8 approximately equal to 10:1). The results support the role of lymphocytotoxicity in the establishment of the RAS lesion and may suggest a local immunoregulatory imbalance. NK cells, Leu-7 positive, were also identified in the preulcerative lesions and very early ulcerative lesions.

The Welch Allyn AudioScope is a new screening instrument that allows both audiometric testing at 500, 1000, 2000, and 4000 Hz at 25 dB hearing level and otoscopic examination. Sixty-eight patients between 3 and 9 years of age with normal hearing or a variety of hearing losses comprised the study population. Immediately after receiving an audiologic evaluation the subjects were screened with a traditional screening audiometer and two examinations with the AudioScope, performed in a clinic examining room by pediatricians and nurse practitioners unaware of the children's hearing status. The AudioScope was as accurate as traditional hearing screening in identifying children with normal hearing and those with hearing loss. Log-linear modeling demonstrated that the results of AudioScope testing were similar to those of traditional hearing screening. However, the false positive rate was higher at 500 Hz for the first AudioScope examination, suggesting the need for two AudioScope tests. The AudioScope was quick and easy to use, nonthreatening to the subjects, less expensive than a pure-tone screening audiometer, and does not require a sound-treated room.

In cat, a small tympanic membrane (TM) perforation produces a low-frequency loss--in terms of sound pressure changes (deltaSP) in front of the TM re a 10-micronV round window cochlear microphonic (RW CM)--that varies inversely with frequency at a rate of 12dB/octave with a surgically shortened external auditory meatus (EAM). Losses were determined at the outer opening (deltaSP00) and at the TM (deltaSPTM) of four artificial EAM's of various lengths, volumes, and leakiness. In the low-frequency region, a leaky EAM produced a flat loss. In the midfrequency region, the flatness of losses was attributable to (1) the length of the EAM and (2) the location at which the loss was determined. EAM volume was not related to the configuration of the loss. Losses, under all conditions, were always identical in shape and magnitude for the open and closed systems. Clinically, hearing losses due to TM perforations are essentially frequency independent, especially in the low frequencies. The relation between voltage changes (deltaV) across the transducer and losses with different EAM's suggests that the discrepency between audiometric results and CM losses--at least in the high and midfrequencies--may be due to the use of precalibrated SPL's in clinical audiometry.

Between 1978 and 1983, at least 20 children with fluoride poisoning were admitted to two major children's hospitals in Brisbane. Data on telephone calls received by Poisons Information Centres in Australia about fluoride toxicity show that Brisbane, the water supply of which is not fluoridated, received approximately twice as many calls per head of population as were received in Sydney and Melbourne. Concern is also expressed at the standard of packaging of fluoride tablets currently marketed in Australia. A treatment plan for cases of acute fluoride poisoning after oral ingestion is presented.

Various doses of sodium fluoride (NaF), salmon calcitonin (CT) and NaF combined with CT were given intravenously to rats (236 +/- 2 g). Blood plasma samples were collected at various times up to 24 hours and measured for total calcium (adjusted for variation in plasma albumin), inorganic phosphate, ionic fluoride, urea, and creatinine. Following injection of NaF alone, significant hypocalcemia and hyperphosphatemia was observed. In contrast, CT injections resulted in hypocalcemia and hypophosphatemia. NaF and CT given in combination generally resulted in the hypocalcemia being equal to or greater than that calculated from the simple addition of their individual effects. Significant increases in both plasma creatinine and plasma urea were observed following treatment with NaF alone or with CT and NaF together, whereas CT alone had negligible effect. These results suggest that NaF does not mimic the effects of CT; rather that NaF and CT interact to modify their individual effects. The influence of NaF probably occurs via an effect on kidney function.

The advantages and disadvantages of three types of earphones for audiometric testing are discussed. Supraaural earphones continue to be recommended for this purpose, in preference to circumaural and insert types.

This is a preliminary report about the acoustic characteristics of the external ears of infants. A technique was developed to insert a probe tube that is attached to a miniature microphone into the external auditory canals of sleeping infants. The inlet to the microphone was positioned in the lateral half of the external auditory canal. A diffuse sound field (spectral density of approximately 45 dB SPL) was introduced. The microphone output was recorded, and its Fourier Transform was computed. Diffuse-field-to-ear canal sound pressure level transformations were determined for infants ranging in age from newborn to 37 months. Representative sound pressure level transformations are presented. These are shown to vary systematically with the age of the child. The resonance frequency of the external ear is high in the newborns and declines with age. The asymptotic value (approximately 2,700 Hz) is reached during the second year of life. These findings have potential implications for fitting hearing aids on infants and children.

Over a 24-h period, Wistar rats from 4 litters, 6 to 9 days old, were given five intraperitoneal injections of a solution of 0.9% sodium chloride containing sodium fluoride (3 mg F/kg body weight). Within-litter controls were used. All rats were killed by decapitation 2 h after the final injection and the rat heads, cut sagittally, were processed for protein histochemistry. The intensity of staining of the protein in the enamel matrix of the upper jaw molar tooth buds was quantified using the two-wavelength method of microphotometry. A significant increase in the intensity of staining of fluoride-treated tissues over controls was observed with the histochemical methods specific for arginine (P less than 0.01), tyrosine (P less than 0.05), and cysteine (P less than 0.05). Other histochemical methods specific for amino acid groups failed to show any significant difference between fluoride and non-fluoride-treated enamel matrix.

Several recent studies have demonstrated that the ER-3A insert earphone may sometimes be directly substituted, without recalibrating, for a TDH-39/MX-41AR earphone. However, most available data have not been reduced to a form suitable for establishing a revised estimate of the reference threshold levels. This article reports such a data analysis performed on the results of five recent studies. The mean data from the five studies are typically within 1 dB of the provisional reference threshold SPLs given by the ER-3A manufacturer for calibration in a (HA-1) 2-cc coupler. After converting the mean data to equivalent Zwislocki-coupler-type ear simulator SPLs at each of the reported audiometric frequencies (125, 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz), agreement within 1.5 dB was seen with the revised estimate of minimum audible pressures given by Killion [J. Acoust. Soc. Am. 63, 1501-1508 (1978)]. Either the manufacturer's provisional SPLs or the average results from this study may be used with little noticeable difference for most purposes.