Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis.

Leri-Weill Dyschondrosteosis (LWD; OMIM 127300) is a dominantly inherited skeletal dysplasia characterized by disproportionate short stature with predominantly mesomelic limb shortening. Expression is variable and consistently more severe in females, who frequently display the Madelung deformity of the forearm (shortening and bowing of the radius with dorsal subluxation of the distal ulna). The rare Langer Mesomelic Dysplasia (LD; OMIM 249700), characterized by severe short stature with hypoplasia/aplasia of the ulna and fibula, has been postulated to be the homozygous form of LWD (refs 4-6). In a six-generation pedigree with LWD, we established linkage to the marker DXYS6814 in the pseudoautosomal region (PAR1) of the X and Y chromosomes (Z max=6.28; theta=0). Linkage analysis of three smaller pedigrees increased the lod score to 8.68 (theta=0). We identified submicroscopic PAR1 deletions encompassing the recently described short stature homeobox-containing gene SHOX (refs 7,8) segregating with the LWD phenotype in 5 families. A point mutation leading to a premature stop in exon 4 of SHOX was identified in one LWD family.

Evaluation of larvicides in developing management guidelines for long-term control of pest blackflies (Diptera: Simuliidae) along the Orange River, South Africa.

In 2000 and 2001 Orange River levels were higher than normal: associated serious outbreaks of blackfly had a substantial detrimental impact on the local economy. The poor control was attributed to the suspected development of larval resistance to temephos. A long-term solution to blackfly control, through the identification of a suitable replacement to temephos for use during high flow conditions, was proposed. This study, however, failed to identify or register a suitable larvicide for use during high flow conditions. Although permethrin was highly effective against blackfly larvae, it was rejected because of its detrimental impacts on non-target fauna. Various formulations of locally produced dry Bacillus thuringiensis var. israelensis (B.t.i.) were tested, but these were ineffective against blackflies. The study also confirmed that resistance to temephos has developed among Simulium chutteri in the middle and lower Orange River. The feasibility of "reversing" the resistance to temephos through the use of the synergist piperonyl butoxide (PBO) was investigated, but the results were not favourable. Furthermore, PBO was highly toxic to blackflies and non-target organisms, and was not recommended for further testing. This means that B.t.i. currently remains the only symptomatic measure of treatment currently applied. Although resistance to B.t.i. has not been reported for blackflies elsewhere in South Africa, there is a need to remain vigilant and to implement an operational strategy that minimizes the risks of resistance developing.

Visual acuity loss in retinitis pigmentosa. Relationship to visual field loss.

We compared visual acuity with visual field radius in 235 patients with typical retinitis pigmentosa and no evidence of other visual acuity-limiting problems (such as cataract or foveal cystoid edema). Results show a strong relationship between visual acuity loss and proximity to the fovea of the visual field border (shortest distance from the foveal center to the border of the V-4-e isopter) for these patients. Ninety-six percent of patients with central visual field radii greater than 30 degrees have visual acuities of 20/40 or better; 32% of patients with central visual field radii smaller than 10 degrees have visual acuity of 20/40 or better.

Trisomy 22 and intersex.

Complete trisomy 22, with or without mosaicism, has been reported as a distinct syndrome. In this report an infant is described who was externally male but with female rudimentary internal organs and whose karyotype was 47,XX+22.

Use of dental X rays on postirradiated patients with head and neck cancer.

As cancer therapy becomes more successful and cancer survival rates increase, the dentist will be treating more patients who have received radiation therapy for head and neck cancer. Occasionally, patients and health professionals have indicated a belief that patients who have received irradiation to the head and neck regions should not be subjected to additional radiation through dental diagnostic X-ray exposures. A literature search failed to find any references that specifically addressed this question. This study reflects the opinions of 278 radiation oncologists (400 surveyed) who responded to questions about contraindications of dental X rays for the patient with head and neck cancer.

An unusual presentation of Smith-Magenis syndrome with iris dysgenesis.

A boy who presented with iris dysgenesis is described. He was shown to have Smith-Magenis syndrome with a deletion of 17p11.2.

A rapid method of estimating the abundance of immature blackflies (Diptera: Simuliidae).

A ten-point visual method of estimating the abundance of immature blackflies in the field is proposed and tested. The method is based on the comparison of larvae and pupae found on natural substrates, with ten diagrammatically prepared abundance classes. When estimates were based on the abundance of blackflies within a 4 x 4 cm area of highest density, there were no significant differences between estimates based on the ten-point visual method and those based on actual counts (P > 0.05). The time taken to assess the abundance of larval blackflies on 30 substrates was about 15 min, depending on substrate accessibility. Personal bias was assessed independently by four people, and was negligible when estimates were based on the highest densities within a 4 x 4 cm quadrat. The method tends to overlook very small larvae, and is not recommended for estimating overall population densities. However, the method provides a reliable, practical and rapid index of blackfly abundance suitable for use in blackfly control programmes.

Control of pest blackflies (Diptera:Simuliidae) along the Orange River, South Africa: 1990-1995.

The efficacy of Bacillus thuringiensis var. israelensis (B.t.i.) and temephos in controlling the pest blackfly Simulium chutteri Lewis along the middle Orange River between 1990 and 1995, was assessed. Larvicides were applied by helicopter to rapids and riffles between Hopetown and Onseepkans, a river distance of 807 km. Larvicidal efficacy was based on the change in larval abundance at selected sites before and after each treatment. The success of the control programme was assessed independently by local farmers, who ranked adult blackfly annoyance on a 4-point scale. Before treatment, blackfly annoyance showed consistent peaks in spring, and sometimes in autumn, and levels were unacceptably high for between 17 and 36 weeks of the year. After treatment started, blackfly annoyance levels were reduced significantly. The number of annual treatments necessary to reduce blackfly annoyance to acceptable levels was highly variable (3-13), and depended on river conditions, as well as the efficacy and timing of each treatment. During low-flow conditions (< 50 m3/s), applications became increasingly difficult in braided sections of the river, and dosage calculations were inaccurate because of local abstraction and return flows. Both larvicides worked well in winter (water temperature 11-13 degrees C). Control of the spring outbreak can be planned well in advance, with the first treatment starting in mid July. A flexible protocol is required to control outbreaks at other times of the year. We recommended the use of B.t.i. for most applications, with increased dosages during algal blooms (> 1500 cells/ml). The use of temphos in the Orange River should be considered only during algal blooms or when flows exceed 300 m3/s. We conclude that helicopter application of larvicides is an effective method or controlling blackflies, along the middle Orange River.

Use of impact testing to predict softness, cow preference, and hardening over time of stall bases.

The objective of this study was to assess the softness and durability of commercially available free-stall bases, and to determine the relationship of stall base softness to cow preference. Clegg impact values were recorded at the University of Wisconsin-Madison Arlington Agricultural Research Station on June 19, 2002, and again on July 24, 2003. The Clegg Impact Soil Tester (model 95051, Lafayette Instruments, Lafayette, IN) with a 20-kg hammer was used in this study. The impact of the hammer on the free-stall base results in a digital display based on peak deceleration of the hammer's impact with the free-stall base in tens of gravities (CIV/H). The CIV/H value, as measured by the Clegg Impact hammer, is based on peak deceleration of the 20-kg hammer's impact with the surface, from a height of 30 cm. Clegg impact measures were highly correlated with cow preference measurements. This relationship suggests that Clegg impact measures of compressibility were good indicators for predicting stall-base acceptance. A cork mattress, 4 foam mattresses, 4 rubber mattresses, 4 rubber mats, and a waterbed were evaluated in this study. Foam-based mattresses lost cushioning ability faster than rubber mattresses or rubber mats. Clegg impact values increased over the 13-mo time period for most stall base types, which indicated a tendency of stall bases to harden.

Chiasma-derived genetic lengths and recombination fractions: a reciprocal translocation 46,XY,t(1;22) (q32;q13).

The chiasma distribution in a human male carrier of a balanced reciprocal translocation 46,XY,t(1;22) (q32;q13) has been compared with data from six controls. The translocation carrier shows a raised chiasma frequency and altered chiasma distribution in chromosome 1, particularly in the region adjacent to the breakpoint. These changes are expected to distort the recombination pattern, implying that caution should be taken when trying to incorporate linkage data from translocation families into the normal genetic map.

Changes in the form of Arrhenius plots of the activity of glucagon-stimulated adenylate cyclase and other hamster liver plasma-membrane enzymes occurring on hibernation.

1. Arrhenius plots of the glucagon-stimulated adenylate cyclase, 5'-nucleotidase, (Na+ + K+)-stimulated adenosine triphosphatase and Mg2+-dependent adenosine triphosphatase activities of control hamster liver plasma membranes exhibited two break points at around 25 and 13 degrees C, whereas Arrhenius plots of their activities in hibernating hamster liver plasma membranes exhibited two break points at around 25 and 4 degrees C. 2. A single break occurring between 25 and 26 degrees C was observed in Arrhenius plots of the activities of fluoride-stimulated adenylate cyclase, basal adenylate cyclase and cyclic AMP phosphodiesterase of liver plasma membranes from both control and hibernating animals. 3. Arrhenius plots of phosphodiesterase I activity showed a single break at 13 degrees C for membranes from control animals, and a single break at around 4 degrees C for liver plasma membranes from hibernating animals. 4. The temperature at which break points occurred in Arrhenius plots of glucagon- and fluoride-stimulated adenylate cyclase activity were decreased by about 7--8 degrees C by addition of 40 mm-benzyl alcohol to the assays. 5. Discontinuities in the Arrhenius plots of 4-anilinonaphthalene-1-sulphonic acid fluorescence occurred at around 24 and 13 degrees C for liver plasma membranes from control animals, and at around 25 and 4 degrees C for membranes from hibernating animals. 6. We suggest that in hamster liver plasma membranes from control animals a lipid phase separation occurs at around 25 degrees C in the inner half of the bilayer and at around 13 degrees C in the outer half of the bilayer. On hibernation a change in bilayer asymmetry occurs, which is expressed by a decrease in the temperature at which the lipid phase separation occurs in the outer half of the bilayer to around 4 degrees C. The assumption made is that enzymes expressing both lipid phase separations penetrate both halves of the bilayer, whereas those experiencing a single break penetrate one half of the bilayer only.

Lysophosphatidylcholines can modulate the activity of the glucagon-stimulated adenylate cyclase from rat liver plasma membranes.

1. Synthetic lysophosphatidylcholines inhibit the glucagon-stimulated adenylate cyclase activity of rat liver plasma membranes at concentrations two to five times lower than those needed to inhibit the fluoride-stimulated activity. 2. Specific 125I-labelled glucagon binding to hormone receptors is inhibited at concentrations similar to those inhibiting the fluoride-stimulated activity. 3. At concentrations of lysophosphatidylcholines immediately below those causing inhibition, an activation of adenylate cyclase activity or hormone binding was observed. 4 These effects are essentially reversible. 5. We conclude that the increased sensitivity of glucagon-stimulated adenylate cyclase to inhibition may be due to the lysophosphatidylcholines interfering with the physical coupling between the hormone receptor and catalytic unit of adenylate cyclase. 6. We suggest that, in vivo, it is possible that lysophosphatidylcholines may modulate the activity of adenylate cyclase only when it is in the hormone-stimulated state.

Chiasma derived genetic maps and recombination fractions: chromosome 13 with reference to the proposed 13q14 retinoblastoma locus.

Provided that there is no chromatid interference, no movement of chiasmata, and no discrepancies between meiotic and mitotic chromosome lengths, then genetic maps and recombination fractions may be directly derived from our meiotic chiasma distribution data. This is illustrated by male chiasma derived genetic lengths and recombination fractions along chromosome 13. The recombination fraction between 13p fluorescent markers and the proposed retinoblastoma locus at 13q14 is estimated at 0.27 to 0.37 and preliminary female chiasma studies suggest a recombination fraction of 0.5 between these two sites. Therefore, it seems unlikely that 13p fluorescent markers may be of any practical help in identifying retinoblastoma gene carriers. This is also borne out by the discordant segregation which has been found in six out of seven retinoblastoma families, which gives a calculated recombination fraction of 0.39 (SE 0.15), not significantly different from 0.5.

Removal of within-cow differences between morning and evening milk yields.

Methods were explored for removing within-cow differences between a.m. and p.m. milk yields to allow direct comparison of consecutive milk yields. Daily a.m. to p.m. ratios of milk yield were studied for 504 lactations of 310 Holstein cows. Ratios varied within lactations and among cows. When the incomplete gamma function was used to characterize lactation curves, 89% of the variation in individual milk yields was explained when an a.m.-p.m. term was included. The a.m. to p.m. ratios increased over the course of lactations. Within-cow adjustment factors for a.m.-p.m. milking, based on weighted and unweighted averages of previous a.m. to p.m. ratios, changed as lactation length increased. A weighted moving average technique, which weighted the last a.m. to p.m. ratio by .15, compared with .85 for previous ratios, was considered to be the optimal method of calculating a factor for removing a.m.-p.m. effects.

Localization of the Surfeit gene cluster containing the ribosomal protein gene L7a to chromosome bands 9q33-34.

The Surfeit gene cluster which contains at least four very tightly spaced unrelated genes, one of which encodes the ribosomal protein L7a, has been localized by an analysis of somatic cell hybrids to the long arm of chromosome 9. By the use of in situ hybridization the Surfeit locus has been further mapped to 9q33-34.

Investigation of factors affecting voluntary and involuntary culling in expanding dairy herds in Wisconsin using survival analysis.

Trends in the relative risk of voluntary culling of low-producing cows and involuntary culling of high-producing cows were examined in 186 Wisconsin dairy herds that expanded significantly between 1994 and 1998. A Weibull model for survival analysis was applied to data of 72,456 Holstein cows with first calving from 1981 to 2000; this model included a time-independent effect of age at first calving and time-dependent effects of year-season, age-parity, and within herd-year quintile for combined fat + protein yield (by time period). The relative risk of (involuntary) culling of high-producing cows (versus average cows) increased from 0.5 in 1981 to 1989 to 0.68 in 1996 to 2000. Meanwhile, the relative risk of (voluntary) culling of low-producing cows decreased from 4.20 to 2.55 over the same time period. Variables related to facilities, labor, and management were obtained via survey, and the relative risk of culling for high-and low-producing cows after expansion (1996 to 2000) was calculated for different levels of each variable. Herds with fewer cows per employee and a greater percentage of labor supplied by family members tended to have lower risk of involuntary culling of profitable cows. Likewise, high-producing cows in herds with fans, sprinklers, self-locking manger stalls, palpation rails, and maternity pens had a significantly lower risk of culling than cows in herds without such facilities. Herds that used 100% artificial insemination (AI) had lower risk of involuntary culling than non-AI herds or herds with a cleanup bull, but 3x milking and use of a custom heifer grower led to unfavorable trends in involuntary culling. In summary, this study documented the unfavorable trends in voluntary and involuntary culling in expanding herds and quantified the gains producers can expect in cow survival by investing in improvements in facilities, labor, and management.

Feeding behavior, milking behavior, and milk yields of cows milked in a parlor versus an automatic milking system.

This study compared feeding and milking behavior and milk yields for cows housed in the same barn, fed the same ration, but milked with a conventional milking parlor (parlor) or automatic milking system (robot). Behavioral data were videotaped hourly 1 d/mo for 9 mo. Feeding behavior patterns differed and were more variable for parlor cows than for robot cows. Both groups had low feeding rates at night and early morning. Feeding activity increased after milking and feed delivery for parlor cows. Milking and feeding activity in the robot system increased after human intervention at 7 a.m.; feed bunk activity peaked 3 h later and remained relatively constant from 10 a.m. to 8 p.m. Percentages of cows at the feed bunk were significantly greater for robot cows than parlor cows only at 10 a.m. and 9 p.m. Batch milking of parlor cows with free access to feed, vs. sequential milking of robot cows, with restricted movement to feed by a one-way gate system, resulted in higher peak percentages of cows at the bunk for parlor cows. Lower, more consistent percentages of cows eating at one time suggests that less bunk space may be needed for cows in robotic milking systems. Higher percentages of cows were observed in the robot from 8 a.m. to 1 p.m. and again from 3 to 7 p.m. Percentages of cows in the robot holding area were greatest from 8 to 11 a.m. and 3 to 6 p.m. and were lowest from midnight to 6 a.m. Milk production over 39 d in summer for subsets of cows was slightly but significantly higher (26.4 vs. 25.8 +/- 0.2 kg/d) for cows in the robot group. Milking frequency, days in milk, parity, and maximum air temperature for 3 d (-2 d to day of observation) affected milk yield comparisons. Results have implications for design of feeding and handling facilities used with automated milking systems.

Risk of HIV infection from blood transfusion in Montreal.

OBJECTIVES: To determine the incidence (including associated donor characteristics and time trends) of HIV infection among repeat blood donors and to estimate the risk of HIV transmission from blood transfusion in Montreal and in Canada as a whole. DESIGN: Retrospective cohort analysis. SETTING: Montreal Centre Blood Transfusion Service. PARTICIPANTS: People who donated blood at least twice after Nov. 1, 1985, and at least once from Apr. 1, 1989, to Mar. 31, 1993. INTERVENTION: Blood was screened for HIV by enzyme-linked immunosorbent assay and results were confirmed by Western blot analysis. OUTCOME MEASURES: Incidence density (the incidence rate per person-time) of HIV infection among repeat blood donors by sex, age group and region of residence, and incidence density and risk among first-time donors and for Canada as whole. RESULTS: There were 200,196 eligible donors and 432,631 person-years (PY) of observation. From 1989 to 1993, there were 18 HIV seroconversions among repeat donors. The crude incidence density was 3.3 per 100,000 PY (95% confidence interval [CI] 1.8 to 5.4 per 100,000 PY); it was 4.9 per 100,000 PY among men and 0.61 per 100,000 PY among women. Age-specific incidence per 100,000 PY was 2.5 among those 12-29 years of age, 5.1 among those 30-49, 2.9 among those 40-49, and 1.4 among those 50 and older. Based on an estimated mean "window period" (from when a donor's blood is capable of transmitting HIV until detectable antibody appears) of 25 days, the current risk of HIV infection from repeat donors in the window period is estimated at 1 in 440,000. Inclusion of blood units from first-time donors produces an overall risk of 1 in 390,000 (95% CI 1 in 250,000 to 655,000). The estimated risk per blood unit in Canada as a whole is 1 in 913000 (95% CI 1 in 507,000 to 2,050,000). CONCLUSIONS: This "sentinel" population of repeat blood donors is subject to important trends in HIV spread. Therefore, estimating the incidence density of HIV infection in repeat donors provides insight into the epidemiologic characteristics of HIV infection at minimal expense. As a result of measures to improve blood safety, including HIV testing, the incidence of HIV infection among blood donors in Canada is low and the risk of HIV transmission from transfusion is extremely small, although not zero.