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Plasmas from 30 normals, 46 patients with von Willebrand's disease (vWd) and 17 with hemophilia A were examined for levels of Total Progressive Antithrombin (TPA) and for three Factor VIII-related activities: coagulant (VIII:C), antigenic (VIIIR:Ag) and Willebrand factor (VIIIR:WF). The mean of TPA for the normals was 102.1%, and for the hemophiliacs 102.6% while that for the vWd group was 133.4%. The difference was statistically highly significant. The 1 3 elevation of TPA in vWd was accompanied by reduction to 44% of the average of all the F. VIII activities. The normal TPA in hemophilia A plasmas suggests that the inverse relationship between TPA and F. VIII in vWd is not the result of the reduced coagulant activity.

Hemostasis is the term applied to the process that regulates the loss of blood from the circulatory system following injury. It involves three interrelated physiological mechanisms: constriction of blood vessels, aggregation of blood platelets to damaged subendothelial surfaces, and the formation of fibrin clots. Together these produce the vascular plug that prevents further bleeding. Abnormal function of one or more of the separate mechanisms may result in excessive bleeding or hemorrhage.

Paracoccidioidomycosis is a systemic disease endemic to South America, but rarely recognised in other parts of the world. The patient we describe represents the first case of paracoccidioidomycosis observed in Trinidad.

This paper describes how a research program was conducted in which the temperature rise of mortars and the durability of concrete containing fly ash were studied. The study of the effect of fly ash on the temperature rise of mortars included the use of both ASTM C 618 Class C and Class F fly ashes. Control tests were conducted on mortars containing ASTM C 150 Type I, Type I-II, and Type III cements, and comparison tests were conducted on mortars containing 20, 27.5, and 35 percent fly ash by volume of cement. It was found that the use of Class F fly ash resulted in a reduction in the temperature of the mortar, whereas the partial replacement of cement with Class C fly ash did not lower the mortar temperature, regardless of the type of cement used. Resistance to scaling in the presence of deicing salts and abrasion resistance tests were conducted on concrete samples cast from 21 batches of concrete. Variables studied included fly ash type, fly ash content, and curing conditions. Both ASTM Class F and Class C fly ashes were used to replace 25 or 35 percent of the cement by volume, and curing conditions included combinations of 50, 75, and 100 F with 50 and 100 percent relative humidities.

VWD shows great variability within and between families. In some kindred the affected persons show decreased amounts of an apparently normal VIIIR:Ag. In others, abnormal electrophoretic mobility of VIIIR:Ag has been associated with a defect in the degree of polymerization. Within kindred, expressivity may be so variable that some transmitters have normal laboratory findings. Detection of linkage between VWD and a clearly defined antigenic or biochemical marker might provide the means to make unambiguous diagnoses and to distinguish between the effects of the multiple genes involved in synthesis of VIIIR:Ag.We have examined 4 VWD kindred, using 23 genetic markers. Individuals were classified for VWD using clinical and laboratory data, pedigree information and 2 statistical procedures: D I based on 3 measures of F VIII activity, and D II which also included bleeding time and a subjective index of symptoms. Using D I, a LOD score of 0.66 at a recombination frequency (θ) of 0.20 was found with GPT (glucose pyruvic transaminase). Using D II a LOD score of 0.50 at a θ of 0.25 was found. Most of the evidence of a VWD- GPT linkage was provided by a single kindred. Using D II, evidence suggesting a second linkage was observed between VWD and GLO (glyoxylase) with a LOD score of 1.03 at a 0 of 0.20, all 4 families contributing.The LOD scores reported are suggestive of linkage and warrant further study. Since GLO relates to Chromosome 6 while the chromosomal location of GPT is not known and since GPT and GLO are unlinked, VWD may be genetically heterogeneous, 2 or more loci being involved.Studies to clarify the relationship of VWD to Chromosome 6 are underway using markers known to be linked to GLO.

For four decades, the Draize test has remained the accepted method for evaluating eye irritation. Criticisms center around the inhumane treatment of animals and the irreproducibility of the subjective scoring procedure. The objective of this study was to determine if changes in corneal thickness obtained using a slit-lamp pachometer could be used to replace the Draize scoring procedure and provide a method for quantifying ocular irritation. Twenty-four chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics) were instilled in the conjunctival sacs of rabbits and irritation monitored by Draize scoring and changes in corneal thickness. The Draize procedure was more adept at detecting minor conjunctival damage, but corneal thickness exhibited less variation and increased sensitivity for detection of healing reactions. A significant linear correlation (y = 1.736 chi + 92.883) was established between Draize score and corneal thickness changes with a correlation coefficient (r) of 0.86 and an F-value for regression of 261.3. Using these findings, an ocular irritation ranking system is proposed based upon the percentage of corneal swelling. Ocular irritation potential was ranked for the chemical groups tested (surfactants greater than alcohols greater than ketones or acetates greater than aromatics). Quantitation of ocular irritation from changes in corneal thickness provides objective, numerical data applicable to standard parametric statistical procedures. This should eliminate the subjective bias inherent to Draize scoring and decrease intra-and interlaboratory variability.

Chlorine (Cl2) gas is a potentially lung-damaging irritant which is used in the chemical, plastics, and paper industries. There are no data published using experimental animals on the chronic inhalation toxicity of chlorine. The purpose of this study was to investigate the chronic effects of Cl2 inhalation in Rhesus monkeys (Macaca mulatta). Rhesus monkeys were exposed to concentrations of 0, 0.1, 0.5, or 2.3 ppm Cl2 for 6 hr per day. 5 days per week for 1 year. Pulmonary physiology (pulmonary diffusing capacity and distribution of ventilation), body weights, urinalysis, electrocardiographs, hematology, and clinical chemistry were evaluated monthly during the study. Blood gas evaluations were performed at 3-month intervals during the study. Histopathologic, ophthalmologic, and neurologic parameters were evaluated after the 1-year exposure period. Monkeys exposed to 2.3 ppm Cl2 exhibited signs of ocular irritation during the daily exposures and a superficial conjunctival irritation was present in the 2.3 ppm group after the 1-year exposure regimen. Treatment-induced lesions revealed by histopathology were confined to the respiratory tract. Lesions associated with the nasal parasite Anatrichosoma spp. were present in the region of squamous epithelium of the nasal vestibule and did not interfere with interpretation of Cl2-induced effects. Treatment-induced histopathologic changes were found in the respiratory epithelium of the nasal passages and trachea and were limited to focal, concentration-related epithelial hyperplasia with loss of cilia and decreased numbers of goblet cells in affected areas. These changes in the nose and trachea were focal and mild in monkeys exposed to 2.3 ppm and were not found in all animals in these exposure groups. Tracheal lesions were confined to the 2.3 ppm group. The lesions observed at 2.3 ppm were not present in all animals. At the lower Cl2 concentrations, similar though less prominent respiratory epithelial lesions were observed. The latter changes were very minimal and were confined to the nasal passages of some treated monkeys and one male control animal. The results of this study indicate that 2.3 ppm chlorine acts as an upper respiratory irritant in monkeys, while 0.5 and 0.1 ppm induce changes of questionable clinical significance. Furthermore, the monkey appears to be less sensitive than the rat to chlorine toxicity.

Upper respiratory tract irritation (sensory irritation) by airborne chemicals in animals causes a decrease in respiratory rate with no compensatory increase in tidal volume. This condition is an important respiratory tract defense mechanism. The purpose of this investigation was to determine whether sensory irritation tolerance would develop in F-344 rats following repeated Cl 2 inhalation. Male, F-344 rats were divided into four groups (40 to 50 animals/group) and exposed to 0, 1, 5, or 10 ppm Cl 2 , 6 hr/day, 5 days/week for 2 weeks. Sensory irritation was quantified 16 to 24 hr following the last day of Cl 2 pretreatment by measuring respiratory rate depression during exposure of groups of three to four animals for 10 min to various Cl 2 concentrations (1 to 760 ppm). Concentration-response curves were compared to the curve obtained from rats receiving no pretreatment (naive group). Tolerance was seen after all Cl 2 pretreatments and was greatest in the 10-ppm group. When compared to the non-pretreated group, all Cl 2 -pretreated rats had concentration-response curves with decreased slopes demonstrating increasing tolerance with increasing Cl 2 challenge concentration. The concentration of Cl 2 needed to elicit a reflex decrease in respiratory rate of 50% (RD 50 ) was 25 ppm in non-pretreated rats whereas Cl 2 pretreatments of 1, 5, or 10 ppm increased the RD 50 values to 90, 71, and 454 ppm, respectively. Tolerance development to sensory irritation is important because an organism's ability to perceive the presence or lung damaging concentrations of irritants may be compromised. Since the current threshold limit value for Cl 2 is 1 ppm, indications of tolerance development of rats exposed to Cl 2 at 1 ppm may be relevant to humans exposed repeatedly to this concentration.

Inhalation of chlorine (Cl2) or formaldehyde (HCHO) stimulates the trigeminal nerve endings in the nasal mucosa and results in respiratory rate depression in a concentration-dependent manner. To determine tolerance and cross-tolerance, the concentration-response curves of respiratory depression were compared between naive rats and rats pre-exposed to Cl2 or HCHO. Chlorine tolerance development was time and concentration dependent, being significant following a 1-day (6 hr/day), 10 ppm exposure, and reaching the maximum in 4 days. At 2.5 ppm of Cl2, tolerance was significant only after 10 days of exposure. Rats tolerant to Cl2 also showed cross-tolerance to HCHO. Tolerance to HCHO was observed in rats exposed to 28 ppm for 4 days, but not in groups exposed to 15 ppm for 1, 4, or 10 days. However, significant cross-tolerance to Cl2 was evident following a 1-day exposure to 15 ppm HCHO, with greatest effect seen in the group exposed for 10 days. Tolerance was reduced after a 7-day recovery following a 4-day exposure. Cross-tolerance was reduced also, but to a much lesser extent. These results suggest a common mechanism for tolerance and cross-tolerance development, but different reactive sites may exist for Cl2 and HCHO at the trigeminal nerve endings.

The sensory irritation potential of dimethylamine (DMA) inhalation on male Fischer-344 rats and male Swiss-Webster mice was evaluated by measuring the reflex decrease in respiratory rate. In addition, the six hour LC50 for rats exposed to dimethylamine was established. Groups of 3 or 4 rats and mice were exposed for 10 minutes to concentrations of DMA ranging from 49 to 1576 ppm during which time the respiratory rate was monitored and recorded. Sensory irritation concentration-response curves were obtained and RD50 values (concentration which elicits a 50% decrease in respiratory rate) were determined to be 573 and 511 ppm for rats and mice, respectively. In another set of experiments seven groups of male rats were exposed to concentrations of DMA ranging from 600 to 6119 ppm for six hours. Mortality counts were made during and for 48 hours post exposure. The sic hour LC50 was determined to be 4540 ppm. Histopathologic examination of the respiratory tract revealed concentration related changes ranging from ulceration and necrosis to rhinitis, tracheitis, and emphysema. Overall, DMA was found to be less potent as a sensory irritant than other airborne irritants.

Male F-344 rats were exposed to target concentrations of 2.5, 5, or 10 ppm Cl2 for various amounts of time, after which respiratory and olfactory nasal mucosal tissues were analyzed for changes in total sulfhydryl (TSH) content. No changes in olfactory mucosa TSH content were observed at the maximum Cl2 exposure. Decreases in content of respiratory mucosa TSH were seen after 6 hr exposures to 5 ppm and 10 ppm, but not 2.5 ppm. The concentration of TSH returned to control values 19 hr after termination of exposure. Analysis of TSH changes in concentration × time (CT) studies suggested that decreases in TSH were dependent on the airborne concentration of Cl2 and not on ‘dose’ (the CT product). The results suggest that inhaled Cl2 can oxidize tissue sulfhydryl groups at the point of entry, but not at deeper regions of the respiratory tract.

Factor VIII (F. VIII) in normal plasma: a) shortens the prolonged clotting time of hemophilic plasma (F. VIII coagulant, VIII:C), b) precipitates with heterologous antisera (F. VIII related antigen, VIIIR:AG), and c) together with the antibiotic Ristocetin, aggregates platelets (F. VIII related Willebrand factor, VIIIR:WF). VIII:C has been shown by others to be separable from VIIIR:AG-WF proteins by gel filtration with buffers of high ionic strength. No one has, to our knowledge, clearly separated VIIIR:WF from VIIIR:AG. We seem to have accomplished this by sequential use of two antibodies to F. VIII. The IgG fractions of a precipitating rabbit anti-human VIII and of a human, non-precipitating anti-VIII were separately bound covalently to CNBr-activated Sepharose. The rabbit antibody had a high affinity for VIIIR: AG, but a low affinity for VIII:C and VIIIR:WF. Passage of human plasma over the rabbit antibody column completely removed VIIIR:AG, but not the VIII:C or VIIIR:WF. The VIIIR:AG-free plasma was then sent over the human antibody column which removed only VIII:C. The effluent retained 60% of the original VIIIR:WF activity but had no measurable VIII:C or VIIIR:AG. Bio-Gel A-15 filtration of the VIIIR:WF resulted in elution of the activity in the Vo fractions. These data suggest that the VIII:C, VIIIR: AG and VIIIR:WF activities may exist in plasma as separate entities.

Respiratory tract irritation by chlorine (Cl2) may be associated with tissue sulfhydryl (-SH) oxidation. This study examined the effects of Cl2 on lung -SH content and on the enzymes which maintain non-protein -SH levels, glucose-6-phosphate dehydrogenase (G-6PD) and glutathione reductase (GSSG-RED). Male Fischer-344 rats were exposed to 12 ppm Cl2, 6 hr/day for 1,5, or 10 days. Following Cl2 exposure, rats were sacrificed immediately or after a 3- to 17-day recovery period. A study using pair-fed nonexposed rats was carried out to clarify possible nonspecific malnutrition effects. No alterations in lung protein -SH, nonprotein -SH, G-6PD, or GSSG-RED were observed in rats sacrificed immediately following 1, 5, or 10 days of Cl2 exposure. Rats allowed to recover 3 days following 10 days of Cl2 treatment had a 20% increase in lung -SH above the values for controls fed ad libitum while G-6PD and GSSG-RED activities increased 98 and 39% above controls, respectively. Similar increases in lung -SH, G-6PD, and GSSG-RED were observed after 6 days recovery. Biochemical alterations returned to control values by 10 days recovery. The observed increases in pulmonary -SH, G-6PD, and GSSG-RED were not the result of decreased food consumption. In conclusion, oxidation of lung -SH content immediately following Cl2 exposure was not observed. An increase in lung -SH and enzyme activities during recovery periods may reflect reparative processes subsequent to Cl2-induced lung damage.

Numerous in vitro cytotoxicity assays have been proposed as potential alternatives to the Draize eye irritancy test. The results reported, based upon the rank correlation of ocular irritancy with cytotoxicity, have been encouraging. However, direct calibration of in vivo to in vitro data utilizing several categories of chemicals has not been reported. This study evaluated the use of in vitro cytotoxicity data for predicting the ocular irritancy potential of 24 chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics). BALB/c 3T3 cells were grown overnight, then exposed for 30 min to at least four different concentrations of each chemical (expressed as volume percentage). Linear regression analysis of the log concentration versus percentage of control growth was used to calculate the concentration of toxicant that inhibited the normal growth rate by 50% (GI50). The rank ordering of cytotoxicity based upon the GI50s was surfactants greater than aromatics greater than alcohols greater than ketones or acetates. The larger molecular weight representative of each series (i.e., 2-ethyl-1-hexanol for alcohols) had lower GI50 values than those of the lower molecular weight substances. The GI50 values were then directly calibrated against in vivo ocular irritancy quantitated as percentage corneal swelling following exposure of rabbits to the same test chemicals. A significant linear correlation between cytotoxicity and ocular irritancy was established only for surfactants and alcohols. For acetates, ketones, and aromatics there was little correlation. The overall poor correlation between cytotoxicity and ocular irritancy was attributed to differences in mechanisms of irritancy. The lack of correlation illustrates that in vitro cytotoxicity data cannot be used to predict the ocular irritancy potential of a broad spectrum of chemicals.

Dimethylamine is a widely used commodity chemical, for which there are few chronic toxicity data. Male and female F-344 rats and B6C3F1 mice were exposed by inhalation to 0, 10, 50, or 175 ppm dimethylamine (DMA) for 6 hr/day, 5 days/week for 12 months. Groups of 9-10 male and female rats and mice were necropsied after 6 and 12 months of exposure. No male mice were sacrificed at 12 months due to a high incidence of early deaths in that group. The mean body weight gain of rats and mice exposed to 175 ppm DMA was depressed to approximately 90% of control after 3 weeks of exposure. The only other treatment-related changes were concentration-related lesions in the nasal passages. Two distinct locations in the nose were affected: the respiratory epithelium in the anterior nasal passages, and the olfactory epithelium, especially that lining the anterior dorsal meatus. There was focal destruction of the anterior nasoturbinate and nasal septum, local inflammation, and focal squamous metaplasia of the respiratory epithelium in rats and mice. Mild goblet cell hyperplasia was observed only in rats. The olfactory epithelium exhibited extensive loss of sensory cells with less damage to sustentacular cells. There was also loss of olfactory nerves, hypertrophy of Bowman's glands, and distension of the ducts of these glands by serocellular debris in regions underlying degenerating olfactory epithelium. At the 175-ppm exposure level, rats had more extensive olfactory lesions than mice, with hyperplasia of small basophilic cells adjacent to the basement membrane being present in rats but not mice. After 12 months of exposure to 10 ppm DMA, minimal loss of olfactory sensory cells and their axons in olfactory nerve bundles was observed in the nasal passages of a few rats and mice. These results indicate that the olfactory sensory cell is highly sensitive to the toxic effects of DMA, with minor lesions being produced in rodents even at the current threshold limit value of 10 ppm.

Summary. The three activities associated with factor VIII—coagulant (VIII:C), antigenic (VIIIR:Ag), and platelet agglutinating or Willebrand factor (VIIIR:WF)— have been separated by sequential antibody affinity chromatography, utilizing a rabbit antibody to factor VIII and a spontaneous human antibody to VIII:C. Normal plasma differentially lost its factor VIII-related antigen following passage over the rabbit antibody column. Subsequent passage of the VIIIR:Ag-depleted plasma over the human antibody column resulted in the loss of VIII:C activity, with retention of the Willebrand factor activity, antigen being partially recovered from the heterologous antibody column. These experiments demonstrate that it is possible to separate two of the factor VIII activities, VIIIR:Ag and VIIIR:WF, which are usually regarded as properties of a single molecule.

Inhalation exposure of animals to low concentrations of chlorine (ca. 1 ppm) may be complicated by the formation of chloramines from the reaction of ammonia, evolved from animal urine and feces, with chlorine. To address this problem, ammonia levels were determined by an indophenol method during a 6-hr period, in inhalation chambers using male, Fischer 344 rats under varying conditions of air flow and animal loading. At chamber air flows of 13, 26, or 40 liters/min, ammonia concentrations were obtained at 2, 4, and 6 hr for 1, 3, or 5% animal loading. Ammonia concentrations increased with time, peaking at 6 hr; they increased with increased percentage animal loading and decreased with increased chamber air flow. At 6 hr, for 13 liters/min, and 1, 3, or 5% animal loading, ammonia concentrations were 0.46, 1.91, and 2.42 ppm, respectively. At 40 liters/min, the ammonia levels at 6 hr were 0.22, 0.39, and 1.30 ppm for 1, 3, or 5% animal loading. Chloramines were detected in a chamber containing low concentrations of chlorine and ammonia (ca. 2 ppm each) by using a modified methyl orange method. These results suggest that, depending upon the variables indicated, sufficient ammonia may be evolved from animals in an inhalation chamber to reduce the amount of free chlorine present. Taken in conjunction with the toxic action of chloramines, such reduction may affect the outcome of chronic, low-level exposures to chlorine.

Groups of male Swiss-Webster mice were exposed to concentrations of chlorine varying from 0.7 to 38.4 ppm and to concentrations of hydrogen chloride varying from 40 to 943 ppm. The total exposure time to both gases was 10 minutes. Dose-response curves were plotted for both chlorine and hydrogen chloride, using the percentage decrease in respiratory rate during each exposure as the response reflecting sensory irritation of the upper respiratory tract. The results showed chlorine to be 33.0 times more irritating than hydrogen chloride, with 95% confidence limits of 18.6 and 57.1. Guidelines for obtaining a range of acceptable threshold limit values (TLV) based on sensory irritation of the upper respiratory tract are discussed. It was concluded that the current TLV of 1 ppm for chlorine is the upper acceptable limit, and that the established TLV of 5 ppm for hydrogen chloride lies at the lower limit of the predicted range. The mechanism of chlorine's and hydrogen chloride's sensory irritation may be explained by their reaction with various functional groups in the membranes of the trigeminal nerve endings lining the nasal mucosa.

Exposure of mice to airborne sensory irritants causes a concentration-dependent depression of respiratory rate. The RD50 concentration (that concentration which elicits a respiratory rate decrease of 50%) has been predicted to be an unacceptable occupational exposure concentration due to intolerable sensory irritation and possible respiratory tract injury in humans. The purpose of this study was (1) to determine whether lesions occur in the respiratory tract of Swiss-Webster mice after exposure to the RD50 concentrations of ten sensory irritants and (2) to compare these changes with respect to type and severity. The RD50 values (ppm) of the chemicals studied are as follows: 2,4-toluene diisocyanate (0.4), acrolein (1.7), formaldehyde (3.1), chloropicrin (8.0), chlorine (9.3), sulfur dioxide (117), ammonia (303), hydrogen chloride (309), dimethylamine (511), and epichlorohydrin (687). After exposure of mice for 6 hr/day for 5 days, the respiratory tract was examined for histopathologic changes. All irritants produced lesions in the nasal cavity with a distinct anterior-posterior severity gradient. There was considerable variation in the extent, and nature of the lesions. The lesions ranged from slight epithelial hypertrophy or hyperplasia to epithelial erosion, ulceration, and necrosis with variable inflammation of the subepithelial tissues. Only chlorine, chloropicrin, and epichlorohydrin induced lesions in the lower respiratory tract. These findings give additional support to the potential value of the RD50 model for setting occupational exposure guidelines and predicting the risk of injury to the respiratory tract from exposure to airborne sensory irritants.

Tranquilization using 3 mg/kg of ketamine by intramuscular injection followed by inhalation anaesthesia using halothane was performed on an adult Cape fur seal in order to perform a metatarsal amputation and ophthalmic examination. Ketamine was found to have little effect at the dosage used while halothane proved to be a rapid induction agent providing a safe, continued level of surgical anaesthesia. Variations in cardiac rate and body temperature were recorded during anesthasia and blood was sampled for haematology.

Quantitative immunoradiometric assays (IRMAS) for the coagulant portion of the FVIII complex [VIII: CAg) have recently been described several laborateries (Reisner et al. Thrombosis Research, in press). The antigen detected by these assays is absent or decreased in the plasma of most individuals with severe hemophilia A, Levels of VIII:CAg and FVIII related antigen (VIIIR.Ag) were measured in ten presumably non-hemophiiic samples obtained either by fetoscopy or after abortion. Ratios of VIII:CAg to VIIIR:Ag ranged from .07 to .52 in four samples where both values could be determined. VI11 :CAg could not be detected in four other samples. Three of these also lacked detectable V111R:Ag and were probably diluted with amniotic fluid which has neither VIII:CAg nor VIIIR:Ag. One Sample had 80% VIIIR. Ag in the absence of detectable VIII:CAg. VIII:CAg was detected in six samples with a range of 4 to 50% of an adult normal pool. An aborted male fetus from a potential carrier of severe hemophilia A had an VIII:CAg to VIIIR:Ag ratio of .42 and was probably not affected, The low values of VIII. CAg seen in this preliminary study may be explained by the decrease in antigenicity seen in serum versus plastra samples in our assay. Hence, extreme care in sample preparation and storage must be exercised should this IRMA for VIII:CAg be used in fetal diagnosis of hemophilia A.

We counseled 174 possible or obligatory carriers of hemophilia “A” between January 1975-January 1980. Pedigree information provided a pedigree probability, πC, and blood samples the likelihood ratio favoring carriership (L.R.). The latter was arrived at from 2 bioassays of F. VIII activity (VIII:C & VIIIR:Ag) by linear discriminant analysis. Each consultand received counsel based on a final probability, P(C), produced by combining πC and L.R. Eighty % of the values of P(C) were either very high or very low which meant that clear-cut advice could usually be given. There were 29 obligatory carriers, 16 mothers of sporadic hemophiliacs, 73 sisters of hemophiliacs, and 56 more distant relatives. The individual values of P(C) could be used within each subset of carriers to relate mendelian expectation and observation. There were very few low P(C)s among mothers of sporadics suggesting that almost all were carriers. As a result, we now consider 0.8 to be a conservative πc for mothers of sporadics. Four women with low P(C)s were present among 29 obligatory carriers. This provided an estimate of negative diagnostic error (4/29=14%) and probably represented the effects of “lyonization”. The observedrexpected ratios of high:low P(C)s were normal among sisters of hemophiliacs and second and third degree relatives. Ten % of our consultands were pregnant when first seen. Twelve mothers with low P(C)s produced 11 liveborn, non-hemophilic children, 7 girls and 4 boys. Four with high P(C)s requested amniocentesis; 3 males were discovered and 2 were aborted. Five possible carriers with high P(C)s who had been seen before pregnancy, returned for assistance after becoming pregnant. All 5 requested amniocentesis, and fetoscopy if a male were present, and 4 males were fetoscoped. Two diagnosed as non-hemophilic in utero proved to be normal after delivery. A third could not be diagnosed, but was non-hemophilic at birth. The fourth, a hemophiliac, did not survive the procedure.

The reaction ep{yields}e'K{sup +}{Lambda}(1520) with {Lambda}(1520){yields}p'K{sup -} was studied at electron beam energies of 4.05, 4.25, and 4.46 GeV, using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The cos {theta}{sub K{sup +}}, {phi}{sub K{sup +}}, Q{sup 2}, and W dependencies of {Lambda}(1520) electroproduction are presented for the kinematic region 0.9

The first measurements of differential cross sections for deuteron photo-disintegration at photon energies up to 4 GeV were performed at the Thomas Jefferson National Accelerator Facility early in 1996. Cross section results for D(γ,p)n at proton center of mass angle of 35°, 53° and 90° will be presented. These results are in good agreement with previous measurements at low energy and extend to higher energies where data were previously unavailable. The 90° degree data show behavior consistent with the constituent counting rules up to 4 GeV and are also in fair agreement with the asymptotic meson exchange model. The 37° and 53° data do not show clear signs of counting rule behavior, although a threshold in transverse momentum for the onset of scaling cannot be excluded.

The reaction $\gamma p \to \pi^+K^-K^+n$ was studied at Jefferson Lab using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S=+1 and mass $M=1555\pm 10$ MeV/c$^2$ was observed in the $nK^+$ invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM=26 MeV/c$^2$), and its statistical significance is 7.8 $\pm$ 1.0 ~$\sigma$. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by a chiral soliton model for the $\Theta^+$ baryon. In addition, the $pK^+$ invariant mass distribution was analyzed in the reaction $\gamma p\to K^-K^+p$ with high statistics in search of doubly-charged exotic baryon states. No resonance structures were found in this spectrum., Comment: 5 pages, 5 figures, add references

The differential cross section, $d\sigma/dt$ for $\omega$ meson exclusive photoproduction on the proton above the resonance region ($2.6, Comment: 5 pages, 5 figures

In an exclusive measurement of the reaction $\gamma d \to K^+ K^- p n$, a narrow peak that can be attributed to an exotic baryon with strangeness $S=+1$ is seen in the $K^+n$ invariant mass spectrum. The peak is at $1.542\pm 0.005$ GeV/c$^2$ with a measured width of 0.021 GeV/c$^2$ FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is $5.2 \pm 0.6 \sigma$. The mass and width of the observed peak are consistent with recent reports of a narrow $S=+1$ baryon by other experimental groups., Comment: 5 pages, 5 figures