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Silicon-on-sapphire (SOS) substrates have been proven to offer significant advantages in the integration of passive and active devices in RF circuits. Germanium on insulator technology is a candidate for future higher performance circuits. Thus the advantages of employing a low loss dielectric substrate other than a silicon-dioxide layer on silicon will be even greater. This paper covers the production of germanium on sapphire (GeOS) substrates by wafer bonding. The quality of the germanium back interface is studied and a tungsten self-aligned gate process MOST process has been developed. High low field mobilities of 450-500 cm2/V-s have been achieved for p-channel MOSTs produced on GeOS substrates. Thick germanium on alumina (GOAL) substrates have also been produced.

An atmospheric plasma activation system has been employed to study its application on low temperature wafer bonding. Oxygen activation on PECVD oxide for bonding of temperature sensitive materials shows no pin hole when activating oxide with thickness more than 0.25 microns. Activation on thermal oxide by helium plasma also shows a pin hole free oxide. Bond strength approximately 1000 mJ/m2 is achieved after 250 degree celcius post-bond anneal which is about twice the bond strength of non-activated samples. Multiple UV components from the helium plasma were detected by spectograph. These UV spectra might have contributed to the bond strength enhancement in Si-SiO2 bonding.

Germanium (Ge) has been bonded to fine grain alumina (Al2O3) by means of a polished polycrystalline silicon interface layer. After room temperature bonding and subsequent bond strength annealing at 150 oC for 24 hrs, the germanium layer was ground and polished to 100um. Low temperature Tungsten (W) gate circular geometry devices, W/L = 9, fabricated on this layer exhibited effective mobility values of 150 cm2/Vs. This is much lower than results obtained on equivalent devices on bulk Ge. Improvement in the germanium polish process resulted in transistors with an effective mobility of 415 cm2/Vs, comparable to that of the bulk Ge devices. Low temperature measurement, down to temperatures of 173 K, showed an improvement in device performance resulting in both an increase in effective mobility to 591 cm2/Vs and a decrease in sub threshold slope from 180 mV/dec to 60 mV/dec indicating a reduction in leakage current.

Tungsten gate germanium MOS transistors have been manufactured on bulk germanium platforms. Hole mobility in the range 450 cm2/Vs has been achieved on bulk germanium, but mobility is reduced during the densification of thinner dielectrics at 600C. This may be due to the formation of volatile GeO at the interface during densification. Low temperature measurements of the thinner dielectric device indicate that lattice scattering is dominant at room temperature for the device where the densification was omitted and the excellent subthreshold slopes at low temperatures also indicate devices of good quality.

An atmospheric plasma activation system has been employed to study its application on low temperature wafer bonding. High bond strength (> 2000 mJ/m2) is achieved by oxygen plasma activation on hydrophilic Si-Si and Si-SiO2 bonding at low temperature annealing. This technique has been proved to cause physical damage to thin SiO2 layers (< 0.5 um) creating a high density of pin holes resulting in leaky oxides. When high resistivity substrates are employed the pin holes is reduced by nearly a factor of 7. A germanium disc bonded to plasma treated thin oxide on silicon was electrically connected to the substrate. The atmospheric plasma technique is currently best suited for silicon-silicon bonding, standard SOI, MMIC and MEMS technology.

Al2O3 and HfO2 films were deposited on germanium substrates by atomic layer deposition (ALD) and analyzed by MOS capacitor electrical characterization. In-situ plasma nitridation performed prior to ALD was found to improve the stability of the interface. For Al2O3/GeON/Ge capacitors, a 450degC anneal in nitrogen ambient reduced hysteresis and oxide fixed charge to 90 mV and 1012 cm-2 respectively, with low leakage current density. On the contrary, degradation was observed for un-nitrided Al2O3/Ge capacitors after 300 and 400degC post-metal anneals. HfO2/GeON/Ge capacitors benefitted from a 400degC densification anneal but exhibited degradation after post-metal anneals at temperatures greater than 300degC. This degradation is attributed to the influence of Al electrodes on the HfO2 gate stack. HfO2 is considered to be a suitable material for the gate stack and Al2O3 for the buried dielectric in a GeOI structure.

Hydrogen implantation of germanium is a promising technique for layer transfer. However, both the implantation process, and subsequent heat treatment can create defects in the transferred layer, which detrimentally effect the performance of devices fabricated on these transferred layers. In this study, implanted Germanium wafers were given various anneals and analysed optically and by spreading resistance, to gain insight on the nature of such defects. GeOI layers were produced by thermal splitting of implanted germanium wafers bonded to sapphire handle substrates.

The rapid diffusion of phosphorus and boron in WSi2 has been characterized using a novel Schottky Barrier test structure. Diffusivity of both dopant species was about 4-5 orders of magnitude higher than that reported in polycrystalline silicon. The dopant diffusivity is strongly dependent on the silicide morphology. Diffusivity measured in low temperature pre-annealed silicide is approximately an order of magnitude higher than in silicide pre-annealed at 1050degC. The dopant diffusivity in oxide lined silicide test structures was 3-4.3x10-10 cm2 s-1 at 900degC while polycrystalline silicon lined structures exhibited a higher value at 900degC of 1.5x10-9 cm2s-1. This is attributed primarily to greater segregation of dopant to the oxide-silicon interface compared to the polysilicon-silicide interface. Boron exhibited a higher diffusivity in WSi2 with diffusivity in the range 4x10-9 cm2s-1 - 1x10-8 cm2s-1 at 900degC.

Hospital-acquired catheter-associated urinary tract infection (CAUTI) is one of the first 6 conditions Medicare is targeting to reduce payment associated with hospital-acquired conditions under Congressional mandate. This study was to determine the positive predictive value (PPV) and sensitivity in identifying patients in Medicare claims who had urinary catheterization and who had hospital-acquired CAUTIs.

ABSTRACTWe conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 µg, 300 µg, 1,000 µg or 3,000 µg of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-µg boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 µg of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.

Germanium has been bonded to both single crystal Al2O3 (sapphire) as well as fine grain Al2O3. A germanium to sapphire bonding energy of 3 J/m2 has been measured after a 200 oC bond anneal. Micro voids formed between the germanium/sapphire interface can be removed by employing an interfacial layer of silicon dioxide on either surface. Patterning the sapphire into a grid pattern prior to bonding creates an escape path for trapped gas or moisture allowing micro void free direct bonding to be achieved. Modifying the surface of the fine grain Al2O3 surface with a polycrystalline silicon deposition and polish creates a surface, having an rms roughness of 1.5nm(measured over a 250um square area), suitable for bonding. Techniques employed in the germanium sapphire bonding can then be used in the bonding of fine grain Al2O3 to germanium.

The bonding of plasma enhanced chemical vapor deposition (PECVD) silicon dioxide layers, deposited at 300oC, to thermal silicon dioxide layers is described. The PECVD oxide requires pre-bond annealing and CMP for void free bonding. Post bond annealing for bond strengthening must be performed at a lower temperature than the pre-bond annealing step. Bond strengths of 1J/m2 have been achieved after bond annealing at 400oC. This bonding method can be used in layer/circuit transfer and has been demonstrated with the transfer of a 2um SOI layer from one substrate to another.

We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all‐transretinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d‐dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase‐type plasminogen activator (uPA), tissue‐type plasminogen activator (t‐PA) and plasminogen activator‐inhibitor 1 (PAI‐1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin‐1β (IL‐1β). The mean plasma levels of fibrin d‐dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL‐1β gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL‐1β) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.

Examines the humor in the poems of Allen Grossman. Infectious hilarity of Grossman's reaction to phrases in the ars poetica of William Shakespeare; Comedy of the "Piano Player Explains Himself"; Long poems that set out to be world-descriptions, autobiographies and testaments; Rounded poems in which the Regulator of the World Explains the World.

Previous research on self-control using macaques (Macaca fascicularis) showed these animals have a strong bias for a delayed, larger reinforcer (Self-control) over an immediate, smaller reinforcer (Impulsive). Typical studies of self-control have used a discrete trials methodology with a secondary discriminative stimulus during the delay periods. This results in a greater exposure to the stimulus representing the self-controlled option and may account for some of the early exclusive preference for self-control observed. The present experiment examined self-control bias in three rhesus macaques (Macaca mulatta) while controlling for differential durations of stimulus exposure. Subjects were presented stimuli via a computer monitor and made choices by touching the stimulus at which point both stimuli were removed for the delay periods. All three subjects displayed a nearly exclusive bias for the delayed, larger reinforcer (self-control). These results are consistent with previous studies, despite the variations in methodology and species.

This study was undertaken to compare oral health status of independent community‐dwelling elders with those using long‐term‐care services. Clinical examinations and self‐reported socio‐demographlc data were collected for 2927 older adults living Independently, using home‐care services, or living In nursing facilities. Mean age of dentate participants (n = 2021) was 72.2 years (range, 50–103 years); mean number of teeth, 18.16; mean DFS, 28.86; and mean RCI, 15.23. In multi‐variate analyses, receiving home‐care services or living in a nursing facility was significantly predictive of poorer oral health status with respect to both coronal and root carles. This was also true for ethnic groups other than non‐Hispanic‐white. We concluded that, In a large, multi‐ethnic sample, direct comparisons highlight significant unmet treatment need among users of long‐term‐care services, compared with independent older adults living in the same communities.

Objectives: Guidelines for colorectal cancer screening and surveillance in people at average risk and at increased risk have recently been published by the American Gastroenterological Association. The guidelines for the population at average risk were evaluated using cost-effectiveness analyses. Methods: Since colorectal cancers primarily arise from precancerous adenomas, a state transition model of disease progression from adenomatous polyps was developed. Rather than assuming that polyps turn to cancer after a fixed interval (dwell time), such transitions were modeled to occur as an exponential function of the age of the polyps. Screening strategies included periodic fecal occult blood test, flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy. Screening costs in 1994 dollars were estimated using Medicare and private claims data, and clinical parameters were based upon published studies. Results: Cost per life-year saved was $12,636 for flexible sigmoidoscopy every 5 years and $14,394 for annual fecal occult blood testing. The assumption made for polyp dwell time critically affected the attractiveness of alternative screening strategies. Conclusions: Sigmoidoscopy every 5 years and annual fecal blood testing were the two most cost-effective strategies, but with low compliance, occult blood testing was less cost-effective. Lowering colonoscopy costs greatly improved the cost-effectiveness of colonoscopy every 10 years.

A DNA-based vaccine containing HIV-1 Env and Rev genes was tested for safety and host immune response in 15 HIV-infected asymptomatic patients with CD4-positive lymphocyte counts ≥500/μl of blood and receiving no antiviral therapy. Successive groups of patients received three doses of vaccine at 30, 100, or 300 μg at 10-week intervals in a dose-escalation trial. Some changes were noted in cytotoxic T-lymphocyte activity against gp160-bearing targets. Importantly, enhanced specific lymphocyte proliferative activity against HIV-1 envelope was observed in multiple patients. Three of three patients in the 300-μg dose group also developed increased MIP-1α levels which were detectable in their serum. Interestingly patients in the lowest dose group showed no overall changes in the immune parameters measured. The majority of patients who exhibited increases in any immune parameters were contained within the 300 μg, which was the highest dose group. These studies support further investigation of this technology for the production of antigen-specific immune responses in humans. Copyright 1999 Academic Press.

Substituted tosylmethyl isocyanides (TosMICs) are useful reagents for which no general method of preparation is available. We describe here a high-yielding method for the synthesis of substituted tosylmethyl formamides, which are readily converted to the corresponding isocyanides.

Candida albicansinjected intravenously into rabbits were rapidly cleared from the bloodstream. Organisms injected into a peripheral vein were predominantly cleared by the lungs; organisms injected into a mesenteric vein were largely cleared by the liver. The isolated, perfused rabbit liver avidly cleared candida organisms from buffer perfusate, but clearance was enhanced when the organisms were suspended in heated normal rabbit serum and was most complete when fresh normal rabbit serum was used as the perfusate.

We reviewed chest roentgenograms from 17 persons with confirmed Legionnaires' disease. None of the cases was associated with known outbreaks. Pulmonary infiltrates, usually extensive, were present in all cases. The predominant radiological pattern both on initial roentgenograms and those from the peak of illness was distal air space disease, usually in a segmental or lobar distribution. The lower lobes were involved most frequently. Pleural effusion and volume loss were infrequent. Radiological findings progressed rapidly and often cleared rapidly, although slow clearing was also seen in some cases. Legionnaires' disease should be included in the radiological differential diagnosis of segmental or lobar pneumonia.(JAMA 1981;245:587-590)

Hb Catonsville is an unstable variant in which glutamic acid is inserted into the α-globin chain between Pro-37(C2) and Thr-38(C3). The peptide sequence data are consistent with the DNA sequence of the polymerase chain reaction-amplified fragment of the variant globin gene, which shows the insertion of the triplet codon—GAA—into the mutant α-globin gene. In the normal α-globin gene cluster the codon for glutamic acid is GAG rather than GAA. Thus, there are two features unique to Hb Catonsville, one the insertion of a single residue into the interior of the α-globin chain, and two the presence of the alternate codon for glutamic acid. The experimental evidence suggests that Hb Catonsville may be an example of nonhomologous nonallelic gene conversion, an observation not previously reported in this gene family. The mutation occurs in the critical α1β2interface of the hemoglobin tetramer and leads to a variant with high oxygen affinity, a reduced cooperativity, and Bohr effect.

The medical information, financial, and logistic aspects of a comprehensive computer-based Appointment, Registration, Information System, and Evaluation (ARISE) are analyzed for the management of a family planning program serving 30,000 patients annually. An overview of the existing computer system network is presented with descriptions of the interactive master patient index, the batch appointment process, the management statistics package, and Department of Health, Education, and Welfare (HEW) reporting. Emphasis is placed on the financial

AbstractAndrost-4-en-3-one-17β-carboxylic acid 1was converted to 3-bromo-N-(1,1-dimethylethyl) androsta-3,5-diene-17-β-carboxamide 2by reaction with DMF/oxalyl bromide and quenching into t-butylamine. 2was converted to 3(R=H) by nickel cyanide catalyzed hydroxycarbonylation or palladium (0) catalyzed hydroxycarbonylation.

PurposeWe describe utilization of procedures to reveal recent epidemiologic trends in evaluation and management of benign prostatic hyperplasia (BPH).Materials and MethodsMedicare claims data reflect clinical practice in the vast majority of elderly Americans. The standard 5% beneficiary sample from Medicare claims files for 1991 to 1995 was searched to identify men 65 years old or older with invoices containing diagnostic and procedure codes indicative of prostate disease or lower urinary tract symptoms. Physician/supplier file claims for this sample of patients were used to identify diagnostic and therapeutic procedures relevant to BPH.ResultsDuring these 5 years claims for uroflowmetry peaked in 1993, filling cystometry gradually declined and pressure flow studies increased. Transurethral resection of the prostate decreased 43%, with even steeper reductions for open prostatectomy. The proportion of transurethral resections performed in hospital inpatients ebbed from 96 to 88%. Age specific operative rates for transurethral resection were highest in the ninth decade, and during the 5 years operative rates generally declined more among white than black men of the same age. Although urethrocystoscopy and excretory urography explicitly for BPH decreased markedly, from 1992 to 1995 the proportion of transurethral resections preceded by urethrocystoscopy for any indication increased from 45 to 47%, while excretory urograms were still obtained before 36% of these operations in 1992 and decreased to 26% in 1995.ConclusionsEvaluation and treatment of lower urinary tract symptoms in elderly men in the United States changed rapidly between 1991 and 1995, with a sharp decline in invasive therapy for BPH.

A sensitive and specific reversed passive hemagglutination (RPHA) assay for cholera enterotoxin has been developed. Equine anti-choleragenoid antibodies purified by immunoadsorption were covalently coupled to formalinized sheep erythrocytes, using bis-diazotized benzidine, and the antitoxin-sensitized erythrocytes were shown to agglutinate specifically in the presence of cholera enterotoxin. In a microtiter RPHA assay system, the smallest quantity of enterotoxin that caused hemagglutination was approximately 20 pg. A sensitive assay for antibodies to enterotoxin was also developed, based on inhibition of RPHA. Using such assays, we demonstrated that several nontoxinogenic (tox-) strains of Vibrio cholerae produced small but detectable yields of enterotoxin, 4 to 16 ng/ml, under conditions where the highly toxinogenic strain 569B Inaba produced approximately 16 microgram of enterotoxin per ml. The enterotoxin produced in small quantities by these tox- strains was found to be identical to the enterotoxin from V. cholerae 569B Inaba iv its immunological and biological activities. Strains of V. cholerae that produce intermediate yields of enterotoxin have been obtained by two techniques: (i) as less toxinogenic mutants derived from highly toxinogenic strains and (ii) as more toxinogenic mutants derived from tox- strains. Thus, the yield of enterotoxin in cultures of V. cholerae grown under standardized conditions is is a genetically controlled trait that can be altered by mutation.

The structural genes for heat-labile enterotoxin (LT) are present on plasmid pCG86. Escherichia coli KL320(pCG86), LT was found to be cell associated. LT was present as a soluble protein in sonic lysates of KL320(pCG86). Thirty-one mutants of KL320(pCG86) that produced increased amounts of extracellular LT were isolated. These hypertoxinogenic (htx) mutants were assigned to four phenotypically distinct classes based on the amounts of cell-associated and extracellular LT in early-stationary-phase cultures. Type 1 and type 2 htx mutants produced significantly increased amounts of cell-associated LT. Type 3 and type 4 htx mutants produced normal or decreased amounts of cell-associated LT was similar to that of the wild type. In the mutants of types 1, 3, and 4, the ratios of extracellular to cell-associated LT were higher than that of the wild type and were characteristic for each strain. Cell lysis or leakage of macromolecular cytoplasmic constituents appeared to be significant for release of LT by mutants of types 1, 3, and 4, because supernatants from cultures of these mutants also contained increased amounts of protein and of the cytoplasmic enzyme glucose 6-phosphate dehydrogenase. In all four representative htx mutants, the hypertoxinogenic phenotypes were dependent on chromosomal mutations. The resident pCG86 plasmids were eliminated from the htx mutants of types 2 and 3. After wild-type plasmid pCG86 was introduced into the cured strains by conjugation, their hypertoxinogenic phenotypes were restored. We conclude that chromosomal loci in E. coli KL320 are important in regulating expression of the LT structural genes of plasmid pCG86.

Outbreaks of febrile illness consistent with legionellosis occurred in successive groups of vacationers at an Adriatic resort in 1980. Illness was associated with one of two hotels used by the groups. A cohort study of guests of the suspect hotel revealed 23 cases of febrile illness with pulmonary symptoms, significant antibody titers to Legionella pneumophila, or both, among 291 persons at risk. Two patients died. Attack rates ranged from 0-19% in the nine cohorts of vacationers and were highest among the most elderly. Febrile illness in the last two cohorts of the season was associated with an antibody titer greater than or equal to 128. L. pneumophila was isolated from shower heads in the suspect hotel, but no association was found between showering and illness or seropositivity. Bacteria identified as L. pneumophila by direct immunofluorescence were also found in water from an adjacent hotel and from the outflow from a common well. No cases were associated with the adjacent hotel.

Isolates of Salmonella typhi from 3661 persons in the United States were reported to the Center for Disease Control from 1967 to 1972. Available case reports and carrier lists for the patients from whom the isolates were recovered were reviewed. During this period the yearly number of travel-associated cases rose 270% and, in contrast to indigenous cases, the number of travel-associated ones increased each year. This increase was largely due to cases associated in some way with Mexico. Furthermore, residents of the United States with Hispanic surnames were at higher risk of contracting typhoid in this country than was the rest of the population. Most indigenous cases were in children or young adults and were not linked to recognized outbreaks. Most known typhoid carriers in the United States are elderly women.

In November 1972 an outbreak of gastrointestinal illness occurred at a public school in Stockport, Iowa. One hundred ninety-four (72%) of 269 pupils and 14 (16%) of 23 staff members were affected. The etiologic agent was a strain of Shigella sonnei resistant to multiple antimicrobials. Waterborne transmission of shigellosis was documented epidemiologically and by isolation of the organism from the school water system. Ninety-seven (14%) of 698 of the students' household contacts developed diarrhea, and possible secondary cases also occurred in 3 (9%) of 32 household contacts of school staff.

Pharmaceutical companies frequently receive unsolicited study proposals from a variety of individuals interested in conducting postmarketing studies with their products. A system for handling and funding these proposals has been developed by the Regional Research (RR) Group in the Department of Medical Development-Marketed Products at Glaxo Inc. This group facilitates the processing, review, and follow-up of these proposals. Following committee review, approved studies are supported financially and monitored by the RR Group. The primary purposes for funding these studies are to: 1) support marketed products through publications and presentations; 2) support efforts of sales representatives by providing them with a resource for responding to individuals interested in conducting clinical studies; and 3) encourage development of scientific data that may not conform to established clinical programs. By providing this support, RR makes available a mechanism to sponsor studies not planned by the clinical and marketing groups, but considered interesting and informative. Product visibility and public relations with the medical community are also enhanced through the support and successful completion of these studies.

The role of delta-positive cells in the immune response was studied by comparing the effects of treatment with allotype-specific IgD hybridoma antibody on homozygous BALB/c or SJL/J and heterozygous (BALB x SJL)F1 mice. Homozygous mice, injected from birth with the relevant anti-delta antibody, made primary or secondary immune responses to intravenously injected trinitrophenyl (TNP)-Brucella abortus, TNP-Ficoll, and TNP-keyhole limpet hemocyanin, which did not differ significantly from those of control mice, despite the fact that IgD+ cells were depleted and Ig+ cells were markedly reduced in the spleens of treated mice. Responses in nodes draining a local injection of TNP-Brucella abortus were, however, significantly suppressed. Heterozygous mice, injected from birth with either anti-Ig-5a or anti-Ig-5b, showed a marked reduction in the number cells producing IgG antibody of linked allotype specificity in the secondary response to intravenously injected sheep erythrocytes. A corresponding decrease in the amount of serum IgG2a of that allotype specificity was also noted. However, in agreement with the results obtained in homozygotes, heterozygotes injected simultaneously with anti-IgD directed against each of the allotypes made normal, if not enhanced, plaque-forming cell responses of both allotype specificities. Similarly, serum IgG2a levels were normal in all but one mouse treated in this fashion. These results indicate that IgD+ cells are not essential for an immune response in vivo. Although the delta-positive cell is used preferentially under normal conditions, it appears that an alternative mechanism exists by which, in the absence of these cells, the animal is able to make a normal immune response.

The extent of variability in the number of human hemoglobin (Hb) alpha chain loci has not yet been conclusively determined. There is evidence that in some populations individuals may possess two alpha-chain loci, while in other populations only one locus is present. Electrophoresis of peripheral blood from 53 heterozygotes for Hb G Philadelphia (alpha 68 Asn leads to Lys) revealed that the proportion of Hb G is trimodally distributed, with modes at approximately 20, 30, and 40% Hb G. Familial, hematologic, and statistical studies suggest that hte proportion of Hb G is not random but is genetically controlled and inversely correlated with mean cell volume. Two alternative genetic models are proposed to explain these findings: one assums alpha-thalassemia, while the other postulates variability in the number of alpha-chain loci in the American Black population. Biosynthetic studies of blood from 15 subjects revealed balanced synthesis of alpha and beta globin chains in heterozygotes from all three classes, strongly supporting variable gene dosage rather than alpha-thalassemia as the mechanism underlying the observed trimodality in the proportion of Hb G. Incompatibilities between out results and current concepts of alpha-thalassemia are discussed in the context of differences between Black compared with Oriental and Italian forms of Hb H disease.