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Objectives: The purpose of this study was to examine the time requirements and costs of recruiting older adults for participation in a medical center-/university-sponsored, home-based nutrition education study. A two-step recruitment strategy consisting of an introductory letter followed by a telephone call was used., Design: A random selection of 1300 individuals aged 60 to 74 years was drawn from a patient database of a large, rural, tertiary care hospital to receive introductory letters and recruitment telephone calls. One week after the mailing, potential subjects were contacted by trained interviewers and asked to participate in a home-based nutrition education study., Participants: Men and women, aged 60 to 74 years, whose names appeared in a rural, tertiary care hospital database., Measurements: Recruitment rate, time required for recruitment by telephone, and cost of the combined mailing and telephone recruitment effort., Results: Of the 1300 individuals selected, 1077 (83%) people were contacted by phone and 223 (17%) people were unable to be reached. A total of 2895 calling attempts were required to determine the recruitment status of those identified as potential participants. Of those reached by phone, the recruitment rate was 45%. The total cost (mailing, telephone, and database management) per recruited subject was $8.56., Conclusion: This study has helped to establish the costs of recruitment for home-based education interventions using a two-step strategy of an introductory mailing and follow-up telephone interview.

In our study of the Hearing in Young Adults (HIYA) aged 18-25 years, there appeared to be little effect of social noise on hearing thresholds (Smith et al. 1998). There was however, a threefold increase in the reports of tinnitus in those subjects with significant social noise exposure (>/=97 dB NIL). No other abnormality was found of hearing function for those who were exposed to the most social noise. In an attempt to investigate this further we invited a sub-sample of those tested in the earlier phase of the study, to conduct further examinations of their hearing function. The three groups eventually consisted of those in the most social noise group who reported tinnitus (n=15) and those who did not (n=15), plus a group of people who had no social noise exposure but who reported tinnitus (n=8). All the groups were retested for their hearing thresholds, using standard audiometry and also the Audioscan technique to look for notches in the audiogram. Speech tests were carried out using an adaptive FAAF test. Transient-evoked oto-acoustic emissions were measured and also suppressed with a contralateral broad-band noise. Some evidence has been found to suggest that those young people who reported tinnitus are affected by social noise exposure, in terms of pure tone thresholds, speech tests, oto-acoustic emissions and reported hearing problems. Lessons can be drawn from our attempt to follow up this interesting population. First, the population is highly mobile and follow-up is difficult. Second, the presumed noise exposure was often not appropriate because even after a year it was possible for several individuals with insignificant social noise to move into the group with significant social noise exposure. Third, there is a need for a larger multi-centre study to look at the effect of social noise in more detail using a common protocol. The results of our study will be very useful in calculating the numbers needed in such a multi-centre study.

The pattern of motor (body movement) and autonomic (heart rate and respiration) responses to no sound and sound trials were compared in 20 pre-term and 22 full-term neonates. Sound levels were calibrated using neonatal ear-sized couplers to produce, in the neonatal ear, sound levels of 80, 90 and 100 dB SPL. Accelerations in heart rate (> or = beats per minute for pre-terms; > or = 7 beats per minute for full-terms) were found to be the best criterion for establishing a possible response using bandpass noise at 80, 90 or 100 dB SPL. Respiration rate decreased in response to sound stimuli, this being significant for the pre-term group for the 100 dB SPL stimulus when comparing the 5 s period post-stimulus with the stimulus period. The number of movements detected during the sound trials was higher than for the control trials, being statistically significant for the pre-term group. These changes were elicited in response to stimuli presented at levels some 20-40 dB lower than for other studies and for behavioural screening because sounds were calibrated in an appropriately sized coupler. It is concluded that the response to sound is different in the pre-term group compared with the full-term group.

The change in the performance of the HVDT as targeted neonatal hearing screening has been introduced has been examined for the Nottingham district. The records for all children born in the period 1984-1993 within the district and having a permanent hearing loss of > or = 50 dB in the better ear have been examined. The referral route leading to ascertainment of the hearing loss as well as the result of any screening tests were noted. The data shows an increase in the number referred prior to the HVDT, mainly as a result of neonatal screen failure. At the same time there has been a reduction in the sensitivity of the HVDT from 78% in the first half of the decade to 38% for the second half. There are also some indications of an increase in the coverage and the failure rate over the time. Possible reasons for these changes are discussed.

Studies have implicated defective Ig class switch in the pathogenesis of IgA deficiency. To understand better the molecular events that regulate IgA class switch, a 1.4-kb region of the IgA locus containing the I alpha exon was replaced with a human hypoxanthine phosphoribosyltransferase minigene by gene targeting in murine embryonic stem cells. The I alpha exon-deficient mice derived from these embryonic stem cells had normal IgA levels in serum and secretions and normal numbers of IgA B cells in Peyer's patches and spleen. Further, I alpha exon-deficient B cells efficiently underwent IgA class switch in vitro, despite the absence of I alpha exon-containing germline transcripts. Notably, I alpha exon-deficient B cells did not require TGF-beta for IgA class switch since stimulation with LPS alone led to IgA expression. Nonetheless, whereas I alpha exon-deficient B cells constitutively expressed human hypoxanthine phosphoribosyltransferase transcripts, they did not produce IgA in the absence of LPS stimulation. These results demonstrate that the I alpha exon or transcripts containing the I alpha exon are not required for IgA class switch. Further, the effects of TGF-beta on I alpha locus transcription can be supplanted by expression of a heterologous minigene at that locus, but a second signal is required for the induction of IgA class switch.

Hearing threshold levels at audiometric frequencies between 0.25 and 8 kHz were obtained by manual audiometry using 5-dB steps in adults aged 18-30 years, as part of a large random survey of hearing in the UK. After screening to ensure otological normality, including careful analysis of any noise exposure history, the median thresholds of the 241 screened subjects deviated from audiometric zero by an average of 4.3 dB over the frequencies from 0.5 to 4 kHz in the direction of poorer hearing. Even greater deviations were evident at 0.25, 6 and 8 kHz, consistent with the discrepancies between normal hearing threshold and ISO 389 standard reference zero that have been reported previously. Within the age band from 18 to 30 years, age did not influence hearing threshold levels. Socio-economic status defined by occupational group (manual or non-manual) had a significant effect at frequencies up to 2 kHz, with those in non-manual occupations having better hearing than those in manual occupations by an average of 2.4 dB, despite screening for middle-ear disease, noise exposure and other possibly confounding factors. In a screened sample, males had better hearing threshold levels than females, but this difference was sensitive to screening criteria. The unscreened sample had median hearing threshold levels that were at most 2 dB worse than the screened sample across the frequency range.

This 10 year retrospective study of all causes of bacterial meningitis for children resident in Nottingham District Health Authority area reports an annual incidence rate per 100,000 children aged 0-16 years of 16.0 (95% confidence interval 14.0 to 18.1). There was a steady increase in incidence from 9.6/100,000 in 1980 to 24.3/100,000 in 1989. This was mainly due to an increase in the incidence of meningococcal infections in the age group 1 month to 5 years. Incidence rates varied with age being: 37.2/100,000 (25.9 to 53.5) for 0-28 days of age, 115.5/100,000 (93.9 to 141.9) for 1-11 months of age, 28.5/100,000 (23.1 to 35.3) for 12-59 months of age, and 2.8/100,000 (1.9 to 4.1) for 5-16 years of age. Overall annual mortality incidence per 100,000 was 1.8 (1.2 to 2.8). For the different age groups this was: 10.1 (4.8 to 21.1) for 0-28 days, 11.5 (6.0 to 22.2) for 1-11 months, 1.0 (0.3 to 3.1) for 12-59 months, and 0.4 (0.1 to 1.2) for 5-16 years of age. There were interactions between the type of meningitis and the year of the infection on the mortality rate. Mortality decreased in those with infections caused by bacteria other than Neisseria meningitidis and Haemophilus influenzae.

To directly assess c-myc function in cellular proliferation, differentiation, and embryogenesis, we have used homologous recombination in embryonic stem cells to generate both heterozygous and homozygous c-myc mutant ES cell lines. The mutation is a null allele at the protein level. Mouse chimeras from seven heterozygous cell lines transmitted the mutant allele to their offspring. The analysis of embryos from two clones has shown that the mutation is lethal in homozygotes between 9.5 and 10.5 days of gestation. The embryos are generally smaller and retarded in development compared with their littermates. Pathologic abnormalities include the heart, pericardium, neural tube, and delay or failure in turning of the embryo. Heterozygous females have reduced fertility owing to embryonic resorption before 9.5 days of gestation in 14% of implanted embryos. c-Myc protein is necessary for embryonic survival beyond 10.5 days of gestation; however, it appears to be dispensable for cell division both in ES cell lines and in the embryo before that time.

We have investigated coelectroporation as a method for introducing minor genetic changes into specific genes in embryonic stem cells. A selectable marker (neo) and a targeting replacement vector designed to insert a 4-bp insertion into exon 3 of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene were coelectroporated into embryonic stem cells and selected in G418 and 6-thioguanine (6-TG). HPRT-negative clones were obtained at a frequency of approximately 1 per 520 G418r clones. Southern analysis and the polymerase chain reaction were used to demonstrate that 3 of 36 of the 6-TG-resistant clones had the desired 4-bp insertion without any other disruption of the HPRT locus. Initial studies indicated that the other 33 6-TG-resistant clones probably resulted from the targeted integration of a concatemer containing both the targeting construct and the selectable neo gene.

This study examined the oral language production abilities of a group of young children with bilateral sensorineural hearing impairments (greater than 25 dB HL). The effects of age of intervention-as indexed by age of detection, referral, first appointment and hearing-aid fitting-and of the severity of their hearing impairments on spoken language and communication were the foci of the study. Children were aged between 27 and 80 months with hearing threshold levels ranging from 32 to 98 dB in the better ear. All were audio- and video-taped in their own homes, in an unstructured play setting with the mother. Measures of expressive language ability were extracted including mean length of utterance, vocabulary size, words per min., total utterance attempts per min., proportion of non-verbal utterances and the proportion of questions asked by the child. No significant correlations were found between the children's hearing impairments and their scores on the language measures once age at interview had been statistically controlled. However, significant correlations were found between the language measures and the ages at which the children received intervention for their hearing impairments, in particular for vocabulary and those language measures denoting the rate and quality of the child's interaction during the episode recorded. This finding is consistent with some of the arguments to be found in the small body of data addressing the question of early intervention.

AP17 and AP19 are the smallest polypeptide chain components of AP-2 and AP-1, the clathrin-associated protein complexes found in coated structures of the plasma membrane and Golgi apparatus of mammalian cells. cDNA clones representing the entire coding sequence of AP17 and AP19 were isolated from rat and mouse brain cDNA libraries, respectively. Determination of their nucleotide sequence predicts proteins of 142 and 158 amino acids with Mr 17,018 and 18,733. A sequence comparison of rat brain AP17 with mouse brain AP19 demonstrates that the small chains are highly related. A computer search for other related proteins has uncovered in yeast a previously unknown gene whose DNA sequence encodes a protein homologous to the small chain of AP complexes. The yeast sequence predicts Yap17p, a protein with 147 amino acids and a Mr of 17,373 that is slightly more related to the mammalian AP17 chain than to its AP19 counterpart.

A survey of the use of behavioural methods for neonatal hearing screening in 1985 (1) concluded that the future for automated methods was quite promising. Since then several studies have assessed the two main automated behavioural tests: the Auditory Response Cradle (ARC) and the Crib-o-Gram (COG). As a screen targeted at neonatal intensive care unit (NICU) babies and other high risk groups (at present the most cost-effective form of neonatal hearing screening), the ARC is shown to have low sensitivity, even for severe hearing impairments, and the COG has an unacceptably low specificity. Any future for behavioural testing during this period must therefore rely on new implementations flowing out of a fundamental understanding of (a) the way in which neonates respond to sound and (b) the ways in which a behavioural test might complement screening with Auditory Brainstem Responses (ABR) or Evoked Oto-acoustic Emissions (EOAE). A clearer understanding of the relative benefits of detecting different degrees of hearing impairment at birth in both the NICU population and the unrestricted population is urgently needed. To determine what role should be played by specific screening programmes such benefits need to be balanced against the total costs of screening assessment and rehabilitation, in which false positives (low specificity) play a large part.

Objective: To determine the best means of detecting hearing disability in subjects aged 50-65 and whether rehabilitative intervention is acceptable in this age group., Design: Questionnaire survey of patients on general practice age-sex registers. Two types of questionnaire were used, one being based on the closed set approach of the Institute of Hearing Research questionnaire, which had been used in a pilot study, and the other being a simplified version of this questionnaire developed by the Welsh Hearing Institute and based on open set questions. Questionnaires were sent up to three times, and any patients who had not responded two months after the last posting were personally contacted., Setting: Two general practices in Glyncorrwg and Blaengwynfi in the Afan valley, West Glamorgan., Patients: 271 Patients in Glyncorrwg (136 men, 135 women) and 333 patients in Blaengwynfi (173 men, 160 women) aged 50-65., Interventions: All patients indicating hearing disability in answering the questionnaires were invited to attend for a evaluative session in their village. After audiometric testing advice and arrangements for fitting a hearing aid were offered as appropriate., Main Outcome Measures: Response rates and prevalence of hearing disability before intervention and of possession of hearing aids before and after intervention., Results: After three postings and personal contact the response rate was 98% (266/271) in Glyncorrwg, where the complex questionnaire was used, and 97% (322/333) in Blaengwynfi. The prevalence of hearing disability was respectively 53% (141/266) and 46% (148/322) and the prevalence of owning a hearing aid 7% (19/266) and 8% (24/322). After intervention the possession of hearing aids rose to 24% (64/266) in Glyncorrwg and 22% (71/322) in Blaengwynfi; six months later the aids were being used regularly. A direct comparison of the two questionnaires in 69 subjects from Blaengwynfi showed no significant differences in the amount of disability detected by each one. The first posting of questionnaires detected 65% (189/289) of the hearing disability in the two villages or 78% (72/92) of those prepared to accept hearing aids for the first time; 96% (88/92) of those who accepted hearing aids were detected by two postings., Conclusions: Simple questionnaires are effective in detecting hearing disabilities in people aged 50-65, and intervention was acceptable in many of those who reported having difficulties in hearing. The response rates from successive postings suggest that two postings are sufficient in terms of the return in detecting those who will accept intervention.

Our knowledge of the progression and aetiology of hearing impairments is mainly inferred from cross-sectional studies of populations or individual case studies of relatively rare conditions. Longitudinal studies of carefully stratified samples enable scientific analysis of these two aspects of the ageing auditory system and also provide much needed incidence data on the basis of which to plan comprehensive hearing services. This preliminary paper using data from two studies over relatively short periods (between 2-4.5 years in Great Britain (GB) and up to 8 years in Denmark (DK] confirms (a) that deterioration of hearing impairment appears to be continuous and gradual for the majority (up to 97% on a 2-year assessment) with a median of about 5-6 dB/decade, and (b) that for mid-frequency average hearing levels applied to the samples of average age 55 (range 40-65) the incidence of hearing impairment is predicted accurately by interpolation of the relevant prevalence figures, and runs at about 1.8% per annum for 25+ dBHL bilateral hearing impairments. However, the actual rate of deterioration does seem to be influenced by age, those over 55 showing a high rate of up to 9 dB/decade against 3 dB/decade for those under 55. This implies that study over a much longer time is required to find a more exact form for the relationship between age and the rate of deterioration of hearing impairments.

The nature and scale of services for hearing-impaired people should be formed in the light of the demographic profile of the hearing-impaired. This paper furnishes data for three elements of that profile: the number of hearing-impaired people in England and Wales, the increase in the number of hearing-impaired that might be expected given the growth of the elderly population in England and Wales, and the major factors that influence use of hearing services at present. The combination of reliable prevalence data (1) with demographic information (2) gives good estimates of the numbers of hearing-impaired people and their age distribution. Thus an estimate of 7.4 million people with average hearing thresholds at mid frequencies of 25+ dBHL can be made for an adult population of 38.7 million (aged 18+ years). Eighty percent of these hearing-impaired people are aged over 60 years. Given no change in prevalence rates over the next 20 years, the demographic structure of England and Wales will increase the number of hearing-impaired by approximately 20%. The detailed form of service for the elderly will need to take into account factors shown to put groups at a disadvantage. In particular, the large shortfall in services for the very elderly (over 80 years) and those in manual occupations needs to be addressed.

The records of six hundred and fifty-five patients treated in the Dental Day-Stay Unit over a twelve-month period were reviewed. 2.1% of 95 patients assessed as suitable for day-stay surgery, and 2.2% of 542 patients not assessed prior to anaesthesia were admitted postoperatively. As an index of outcome, 2.56% of 547 day cases were admitted postoperatively, 0.73% being attributable to anaesthesia. Forty-seven day patients were treated in the dental chair, and 108 were treated as inpatients. Over 37% had at least one concurrent medical problem, while 10.4% were mentally handicapped. Guidelines for day-care selection require that the procedure be straightforward, the patient medically fit, be discharged escorted, and live within a reasonable distance of the hospital. From our study, four specific patient groups are identified. These are: the young and healthy, the mentally handicapped, the medically compromised, and those with airway problems.

The C3HfB/HeN (C3Hf) mouse strain expresses an H-2Kk molecule, previously denoted H-2Kkv1, that is structurally and functionally distinct from H-2Kk of the parental C3H strain. By molecular genetic analysis, we demonstrate that the C3Hf H-2K gene carries a homozygous coding region mutation relative to the C3H allele, revealing that C3Hf meets the requirements for assignment of a mutant haplotype, H-2km2. C3Hf H-2Kkm2 bears a single clustered substitution of four nucleotides within 14 contiguous nucleotides in exon 3. Since this sequence also is present intact at the homologous position in H-2Dk of both C3H and C3Hf, the origin of the H-2Kkm2 mutation is consistent with a nonreciprocal sequence transfer from the H-2Dk donor gene, analogous to the mechanism proposed for generation of the H-2Kb mutations. The H-2Kkm2 mutation encodes three clustered amino acid substitutions, at positions 95, 98, and 99, that map to one of the large beta strands at the bottom of the peptide antigen binding cleft of the H-2Kkm2 molecule. The nature and location of these amino acid substitutions are unique relative to any other known H-2 mutant or HLA variant, and underscore the importance of the beta-pleated sheet in influencing CTL recognition. These results indicate that H-2Kkm2 alloantigenicity may derive largely from altered presentation of self cellular peptides.

The health-economic and statistical problems involved in concluding in favour of provision of binaural aids for subsets of the hearing-impaired are outlined. A positive mean binaural advantage is a first step only; an adequate way of handling individual differences must be the second step. Data comparing two population studies show an appreciable binaural advantage for speech in noise; age differentially affects the binaural advantage in males only, which may explain contradictions in the literature. Evidence is obtained that binaural sentence understanding in noise does depend materially upon symmetry of hearing, despite a generally minimal role for the worse ear a statistical predictor. Detailed results suggest that 15 dB asymmetry at threshold should be used as a contraindication to binaural fitting. At lesser degrees of asymmetry (around 10 dB), asymmetry alone is not an adequate basis for generalised differential prognosis for binaural aids because of various supra-threshold considerations. Hence binaural integration should be directly assessed both in field trials of binaural aiding, and in clinical practice.

The conventional model of polymeric IgM depicts a unique structure in which the mu heavy chains and J chain are joined by well defined disulfide bonds involving cysteine residues at positions 337, 414 and 575 of the mu chain. To test this model, we have used site directed mutagenesis to produce IgM in which these cysteines have been replaced by serine. In each case the single mutants were able to assemble polymeric IgM, which was analyzed for its size, morphology, J chain content and activity in complement dependent cytolysis. Whereas normal polymeric IgM is composed predominantly of pentameric and hexameric molecules, the mutant IgM-Ser414 is covalently assembled as pentamers and smaller forms; IgM-Ser575 is assembled as covalent hexamers. IgM-Ser337 appears to include the same pentameric and hexameric forms as normal IgM except that, unlike normal polymeric IgM, most pentameric/hexameric IgM-Ser337 is not covalently assembled. J chain is present in polymeric IgM-Ser337 but absent in polymeric IgM-Ser414 and IgM-Ser575. IgM-Ser414 is defective in activating the classical pathway of complement dependent cytolysis. Our observations are consistent with models in which the covalent linkages between mu chains are mediated by disulfide bonded Cys337-Cys337, Cys414-Cys414 and Cys575-Cys575 but indicate that the arrangement of these Cys-Cys pairs in series and in parallel varies among and within IgM molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

During a 9-day period in August 1980 in a New Jersey hospital, three pairs of consecutively numbered blood cultures from different patients were identified as positive for the same organism (two pairs of Klebsiella pneumoniae and one pair of group A Streptococcus), for each pair, both cultures were positive in the same atmosphere, both organisms had the same sensitivities, and the second of each pair grew at least 2 days after the first and was the only positive blood culture obtained from the patient. When the hospital laboratory discontinued use of its radiometric culture analyzer for 15 days, no more consecutive pairs of positive cultures occurred. Subsequent use of the machine for 9 days with a new power unit but the original circuit boards resulted in one more similar consecutive pair (Staphylococcus epidermidis). After replacement of the entire power unit, there were no further such pairs. Examination of the machine by the manufacturer revealed a defective circuit board which resulted in inadequate needle sterilization. Laboratories which utilize radiometric analyzers should be aware of the potential for cross contamination. Recognition of such events requires alert microbiologists and infection control practitioners and a record system in the bacteriology laboratory designed to identify such clusters.

We have determined the structure and organization of the entire Qa family of class I genes from the major histocompatibility complex of the C3H mouse. Restriction maps of overlapping lambda and cosmid clones reveal that there are only five Qak genes: Q1k, Q2k, Q4k, Q10k and a Q5/9 hybrid, presumably generated by unequal homologous recombination. The resulting deletion of Q6-Q9 is consistent with the Qa-2null phenotype of this mouse strain. We have sequenced the Qak genes, and predict that each may encode a class I molecule with a structure comparable with that proposed for the transplantation antigens. Furthermore, these Qa products should be able to bind peptides and interact with appropriate T-cell receptors. Interestingly, in comparing Qak and H-2k sequences, we find limited evidence of interlocus gene conversion between Qa and H-2 loci, suggesting that the Qa genes are not likely to serve as a reservoir of genetic information for the generation of H-2 diversity within this haplotype.

In order to define the molecular requirements for IgM pentamer formation, we have isolated several mutant hybridomas which produce predominantly monomeric IgM. For one such mutant, 102, we synthesized a cDNA clone of its mu-mRNA, and found an in-frame 39-bp deletion, which thus encodes a mu-chain lacking amino acids 550-562, a region spanning the fourth constant domain and the tail of the mu-chain. To prove that this deletion is sufficient to block pentamer formation, we used site-directed mutagenesis to construct a mu-gene lacking these 39 bp, and have shown that the expression of this altered mu-gene results in the production of monomeric IgM.

Estimates for the prevalence of self-reported hearing disability and measured hearing impairment as a function of age in the adult population of Great Britain (GB) are reported from two 2-stage surveys. The main study was conducted in Cardiff, Glasgow, Nottingham and Southampton, with rigorous audiological assessment at the second stage. A supplementary study used a sample representative of GB with simplified domiciliary audiological assessments. In the main study, neither stage showed any gross bias arising from the particular cities chosen; the estimates from the first stage are free of bias arising from non-response. The estimates from the second stage are relatively free of bias arising from non-attendance. For the present purposes, defining a 'significant' level of hearing impairment as at least 25 dBHL averaged over the frequencies 0.5, 1, 2, 4 kHz, 16% of the adult population (17-80 years) have a bilateral, and about one in four a unilateral or bilateral, hearing impairment. About 10% of the adult population (aged 17+) report bilateral hearing difficulty in a quiet environment.

A post-anaesthetic scoring system is described. The scoring system scores five parameters that may be quickly assessed by the recovery room staff at five-minute intervals. The system was usefully employed for a month's trial and has now been adopted on a full-time basis at this hospital.

Detection thresholds for a 1.0-kHz pure tone were determined in unmodulated noise and in noise modulated by a 15-Hz square wave. Comodulation masking release (CMR) was calculated as the difference in threshold between the modulated and unmodulated conditions. The noise bandwidth varied between 100 and 1000 Hz. Frequency selectivity was also examined using an abbreviated notched-noise masking method. The subjects in the main experiment consisted of 12 normal-hearing and 12 hearing-impaired subjects with hearing loss of cochlear origin. The most discriminating conditions were repeated on 16 additional hearing-impaired subjects. The CMR of the hearing-impaired group was reduced for the 1000-Hz noise bandwidth. The reduced CMR at this bandwidth correlated significantly with reduced frequency selectivity, consistent with the hypothesis that the across-frequency difference cue used in CMR is diminished by poor frequency selectivity. The results indicated that good frequency selectivity is a prerequisite, but not a guarantee, of large CMR.

Polychlorinated biphenyl (PCB) concentrations in clams (Mercenaria mercenaria) and oysters (Crassostrea virginica) from 17 stations of the western and New Bedford Harbor areas of Buzzards Bay, Massachusetts, clearly show that the New Bedford Harbor area is severely polluted. Up to 5 ppm PCBs (dry weight) were found in shellfish tissue. The most likely sources of the PCBs are chronic releases from two electrical component manufacturers in New Bedford. Close proximity of the shellfish to the source of input is indicated by a high relative abundance of the di-, tri-, and tetrachlorobiphenyls. The data suggest that the New Bedford Harbor area should be considered, along with the Hudson River and Chesapeake Bay, one of the major sources of PCB inputs to the northeastern United States coastal area.

The cysteine at position 575 of the immunoglobulin mu heavy chain is thought to provide the only disulfide bonds joining the monomer subunits of mouse polymeric IgM. The importance of this cysteine in the assembly of polymeric IgM was investigated by using site-directed mutagenesis to produce mu chains with serine at position 575. Thirty percent of the secreted mutant IgM was covalently assembled polymer implying that cysteines other than Cys575 can form inter-subunit disulfide bonds. The polymeric IgM lacked J chain, mediated complement-dependent cytolysis and appeared to have a higher molecular weight than conventional IgM pentamers, as judged by sucrose gradient sedimentation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility. Electron microscopy revealed that the mutant IgM molecule contained six subunits. Wild-type IgM, while synthesized predominantly as a pentameric molecule, was assembled in at least two other forms, which were distinguished by their electrophoretic mobility. The apparently higher molecular weight forms of wild-type IgM include hexameric molecules which, like the hexameric mutant IgM, contained much less J chain that the pentameric form and were 20-fold more efficient at activating complement-dependent cytolysis.

The conventional model of IgM structure depicts a unique, array of mu, L and J chains, held together by well-defined disulfide bonds and other interactions. Some, but not all, recent data support this model. Here Ann Davis and Marc Shulman review recent, as well as older, studies of IgM and consider their implications for our understanding of IgM structure and function.

A small fraction of normal IgM is secreted as monomers rather than polymers. We show here that the mu chains of monomeric IgM are glycosylated differently from the mu chains of polymeric IgM and are comparable in their glycosylation to the mu chains from mutant hybridoma cell lines which produce predominantly monomeric IgM. The difference in glycosylation between monomer and polymer mu chains is due to differences in the terminal processing of their oligosaccharides. The glycosylation of the mutant mu chains is not itself responsible for the block in IgM polymer formation.