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Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with mucolipidosis type II (I‐cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence. This case expands the phenotypic spectrum of mucolipidosis type II. Having redefined the diagnosis in one of the original cases of Pacman dysplasia, we suggest that what is called Pacman dysplasia could very well be Mucolipidosis type II (ML‐II) in other published reports. © 2005 Wiley‐Liss, Inc.

Bovine seminal vesicle cytosol contains a low-molecular-weight and thermostable substance which specifically inhibits the binding of testosterone to its cognate receptor. The mass and the ether phospholipid structure of the inhibitor were elucidated by mass spectrometry. Saturation and binding experiments indicate that the inhibitor acts in a dose-dependent and competitive manner, altering the apparent dissociation constant (KD) while maintaining the number of androgen-binding sites (Bmax). Its possible role in the regulation of androgen binding activity is discussed.

The United States is the most important beef tallow producer in the world, supplying ca. 5.5 billion pounds annually. Approximately half of this beef tallow is exported at relatively low prices when compared to other fats and oils. Only ca. 10% of the total is used in domestic edible products. On the other hand, cocoa butter, coconut oil, palm oil, and palmkernel oil are imported oils whose demand for use in food and confectionery products has been increasing over the past few years. The first of these is the most expensive fat in the world. Beef tallow contains specific triglycerides which are also contained in these imported fats and oils. Through modern technology, beef tallow has been fractionated into products which are compatible with or superior to the imported fats and oils. It is visualized that products from fractionated beef tallow can be used as substitutes and extenders to cocoa butter, palm oil, and other fats and oils in the food and confectionery industries. The economic evaluation in this paper, analyzed through time series data and multiple regression techniques, established the past relationships between per capita consumption of confectionery food fat, beef tallow, cocoa butter, adjusted per capita disposable income, and adjusted costs of confectionery, beef tallow, and cocoa butter from 1956 to 1973. The substitutability of fats and oils was evaluated and the potential uses of fractionated beef tallow investigated.

A solution is proposed for the practical problems of regulatory compliance with toxic metals standards that are lower than the method detection limit. Samples of wastewater treatment plant effluent were analyzed for five different metals by four different laboratories. A two-way analysis of variance was used to estimate the standard deviation that was multiplied by the appropriate Student's ttest statistic. The result is the interlaboratory method detection limit (IMDL). The IMDL was then added to the chronic permit limit to find the regulatory compliance limit. Although the values found for silver and mercury were slightly higher than the previously used method detection limit. they did not equal the estimate of practical quantitation limit as previously described in the literature.

Abstract: The United States is the most important beef tallow producer in the world, supplying ca. 5.5 billion pounds annually. Approximately half of this beef tallow is exported at relatively low prices when compared to other fats and oils. Only ca. 10% of the total is used in domestic edible products. On the other hand, cocoa butter, coconut oil, palm oil, and palmkernel oil are imported oils whose demand for use in food and confectionery products has been increasing over the past few years. The first of these is the most expensive fat in the world. Beef tallow contains specific triglycerides which are also contained in these imported fats and oils. Through modern technology, beef tallow has been fractionated into products which are compatible with or superior to the imported fats and oils. It is visualized that products from fractionated beef tallow can be used as substitutes and extenders to cocoa butter, palm oil, and other fats and oils in the food and confectionery industries. The economic evaluation in this paper, analyzed through time series data and multiple regression techniques, established the past relationships between per capita consumption of confectionery food fat, beef tallow, cocoa butter, adjusted per capita disposable income, and adjusted costs of confectionery, beef tallow, and cocoa butter from 1956 to 1973. The substitutability of fats and oils was evaluated and the potential uses of fractionated beef tallow investigated.

We present the clinical, cytogenetic, and molecular studies on a constitutional deletion of 19q ascertained prenatally due to decreased fetal activity and IUGR. Chromosome analysis by GTG banding on amniocytes suggested a del(19)(q13.1q13.3), but the analysis of microsatellites by PCR demonstrated that the deletion involved the distal segment of q12 and the proximal segment of q13.1 (15 cM). The severely affected female infant born at 38 weeks has clinical findings that may be related to haploinsufficiency of specific genes within 19q12.1→q13.1 that control important processes of normal development and cell function. Am. J. Med. Genet. 77:391–394, 1998. © 1998 Wiley-Liss, Inc.

A comparative study was done in women and men of the effects of Δ9-tetrahydrocannabinol (Δ9-THC), intravenously or orally, on dynamic activity, metabolism, excretion, and kinetics. In general no differences between the two sexes were observed. Δ9-THC is converted by microsomal hydroxylation to 11-hydroxy-Δ9-THC (11-OH-Δ9-THC), which is both a key intermediate for further metabolism to 11-nor-Δ9-THC-9-carboxylic acid (11-nor-acid) by liver alcohol-dehydrogenase enzymes and a potent psychoactive metabolite. Major differences in the ratio of the concentration of 11-OH-Δ9-THC to that of Δ9-THC in plasma were found after intravenous dosing (ratio 1:10 to 20) compared with oral administration (ratio 0.5 to 1:1). The final metabolic products are the 11-nor-acids and the related, more polar acids. Urinary excretion of Δ9-THC is restricted to acidic nonconjugated and conjugated metabolites. After 72 hr mean cumulative urinary excretion, noted for both routes and for both sexes, ranged from 13% to 17% of the total dose. After 72 hr the cumulative fecal excretion for both sexes after intravenous administration ranged from 25% to 30%; after oral administration the range was 48% to 53%. Metabolites were found in the feces in large concentration in the nonconjugated form; concentrations of 11-OH-Δ9-THC were particularly noteworthy. Kinetics of Δ9-THC and metabolites were much the same for female and male subjects. For Δ9-THC, terminal-phase t½s for both sexes, irrespective of the route, ranged from 25 to 36 hr. A comparison of the results for AU C i dose (Δ9-THC) after oral dosing with comparable data from intravenous administration indicated bioavailability of the order of 10% to 20% for both sexes. After intravenous Δ9-THC, large apparent volumes of distribution were noted (about 10 l/kg for both sexes).Clinical Pharmacology and Therapeutics (1983) 34, 352–363; doi:10.1038/clpt.1983.179

Recent developments1-3 in the synthesis of 4(1H)-pyridone derivatives have prompted us to communicate a highly versatile synthesis of this class of heterocycles. Acylation of the styrylamine (I)4 (R1 = C2H5) with a substituted arylacetyl halide (II) in ether at Od`-30d`C in the presence of triethylamine or pyridine gave in 2 to 24 hours the enaminoketone (III) (75%-85% trans-isomer together with 25%-15% cis-isomer based on chemical shift of CH methine proton). Enaminoketone (III) could be readily converted to (IIIa) with aqueous methylamine in ethanol or to the bis-enaminoketone (IV) with N,N-dimethylformamide dimethyl acetal. The enaminoketone (IIIa) could be cyclized to pyridone (V) by refluxing with N,N-dimethylformamide dimethyl acetal; alternatively, the bis-enaminoketone (IV) could be cyclized to pyridone (V) by overnight reflux with methylamine hydrochloride in ethanol. yields based on styrylamine were 30%-65%. These transformations are outlined in Scheme 1. As an[image omitted] example, the synthesis of 1-methyl-3-(4-nitrophenyl)-5-phenyl-4(1h)-pyridone (Va) is outlined. Addition of 4-nitrophenylacetyl cloride (0.08 mole) in chloroform (200 ml) to diethylstyrylamine5 (0.08 mole) in chloroform (400 ml) in the presence of triethylamine (0.09 mole, dried over KOH) over a period of 2 hr and under nitrogen atmosphere gave a reddish solution. After stirring an additional hour, the reaction was washed with 1N HC1, N/10 NaOH, and saturated aqueous NaC1, dried over MgSO4, and filtered through Darco-60G to afford on removal of solvent 8.8 g (32%) of the transenaminoketon6 as a crystalline solid from 2-propanol (III, R2 = 4-nitrophenyl, R1 = C2H5; vco 1655 cm-1; δ ppm, 0.97, t, 6H; 3.02, q, 4H; 3.55, s, 2H; 7.72, s, 1H; 7.0-8.1, m, 9H. Anal. Calcd. for C20H22N2O3, % C, 70.99; H, 6.55; N, 8.28. Found: C, 70.84; H, 6.42; N, 8.21 (mp 141°-142°). To 6.0 g of (III) g dissolved in 60 ml of methanol was added 12.0 g of methylamine hydrochloride, and the mixture was heated to reflux for 18 hr. Workup with chloroform gave a quantitative recovery of analytically pure compound (IIIa) as an oil (δ ppm 3.0, d, 3h; 3.53, s, 2H; 6.80, d, 1H; 7-8, m, 9H; Anal. Calcd. for C17H16N2O3, % C, 68.91; H. 5.44; N, 9.45. Found: C, 68.68; H, 5.24; N, 9.20). To 4.85 g of (IIIa) was added 2.14 g (1 equivalent of N,N-dimethylformamide dimethyl acetal and 20.0 ml of anhydrous DMF. The reaction mixture developed an intense blue-violet color which was discharged during refluxing for 16 hr. All volatile components were removed on a rotary evaporator at 80°C/8 Torr to giva a microcrystalline precipitate of the pyridone (Va), which was recrystallized from 2-propanol/DMF to give 3.3 g (66%) of (Va) as bright yellow needles. (vco 1652; δ ppm 3.86, s, 3H; 7.2-8.25, m, 11H; Anal. Calcd. for C18H14N2O3, % C, 70.58; H, 4.61; N, 9.15. Found: C, 70.79; H, 4.89; N, 8.86; mp 212°-214°).

The preceding communication reports on the synthesis of 3,5-diaryl-4(1H)-pyridone derivatives via enaminoketones derived from the acylation of styrylamines with substituted arylacetyl chlorides. In this paper we describe methods for the preparation of 4(1H)-pyridones bearing carboxylic acid, ester, nitrile, cycloalkyl, cycloalkenyl, and derived functional groups in the 3-position.

Three unrelated North American cases with slowly progressive forms of GM1gangliosidosis were found to have two unique point mutations and a 9 bp insertion in the coding region of the gene encoding β-galactosidase. Case 1 was noted to have a 9 bp insertion {CAGAATTTT} on one allele between nucleotides 730 and 731 with no other mutations identified in the other allele. In case 2, two point mutations were found: a unique G→A transition at nucleotide 602 causing an Arg→His substitution in codon 201 (mutation R201H); and a previously identified G→T transition at nucleotide 1527 causing a Trp→Cys substitution in codon 509 (mutation W509C), which has been noted in adult and chronic forms of GM1gangliosidosis. Case 3 had a unique point mutation (A→G transition at nucleotide 797) resulting in a Asn→Ser amino acid substitution in codon 266 (mutation N266S), with no other mutations found in the same or the other allele. Single-strand conformation polymorphism performed on over 100 controls did not demonstrate the presence of the point mutations R201H or N266S. Also, the mutant proteins coded by the two point mutations did not show enzymatic activity in the Cos-1 cell expression system confirming that these mutations are associated with low enzyme activity. ( J Child Neurol1997;12:242—247).

The stress imposed by exercise is usually considered deleterious to patients with cardiopulmonary disorders. For this reason limitation of activity is often recommended for patients with chronic obstructive pulmonary disease. However, Barach and associates 1,2 have repeatedly reported a clinical observation similar to ours, that patients with chronic obstructive pulmonary disease who continue to be active remain in relatively better health for a longer period of time than their more sedentary counterparts. Such observations prompted the present study to assess the physiological responses to progressive exercise training. METHODS Patients with severe obstructive pulmonary disease and evidence of generalized physical disability were selected for the study. Patients with manifestations of left ventricular disease were excluded. In addition, patients who developed either multiple premature ventricular contractions or marked cyanosis during exercise were not included in the study. These latter excluded patients, subsequently trained while breathing supplemental oxygen, will form the basis of

Four patients with the clinical findings of mucolipidosis III were studied. Cultured skin fibroblast cells from three of these four patients were low in each of the five lysosomal enzyme activities measured. The ranges of the enzyme activities in these three patients were as follows: N-acetyl-β-glucosaminidase (11–19 of normal), β-galactosidase (26–33 of normal), α-fucosidase (31–55 of normal), α-mannosidase (53–62 of normal), and arylsulfatase A (16–21 of normal).

Respiratory depression and alveolar hypoventilation require establishment of an airway and mechanically assisted ventilation. A selective respiratory stimulant, vanillic acid diethylamide, produced effective increases of ventilation in 95 of 119 patients with various types of hypoventilatory states. The depth of respiration was increased. The rate was increased also, but to a lesser extent. Prolonged respiratory stimulation was achieved by continuous intravenous therapy in cases of acute depression and by oral administration in convalescent or chronic hypoventilatory states, particularly where aggravated by sleep or by oxygen therapy. This agent was found to be a most valuable adjunct to the management of the patient with severe chronic pulmonary disease and depressed respiration. Side effects were minimal with a wide margin of therapeutic safety demonstrated.

The magnetic field measurements made by the magnetic field experiment on the IMP 3 (Explorer 28) spacecraft have been examined at the time of geomagnetic s.s.c. events. Thirty-six such events occurred while IMP 3 was in the interplanetary medium during 1965, 1966 and 1967 and have been analysed. Of these events 8 must have been tangential discontinuities, 2 are either tangential discontinuities or rotational discontinuities and 26 are possible shock waves. (Two of these 26 events have been shown by other authors to be shocks.) These 26 possible shocks have similar magnetic signatures: an increase of 20 % or more in the magnetic field magnitude and a relatively small (always less than 90°) change in direction. The larger s.s.c. events were more likely to be caused by possible shocks while the smaller events were often associated with tangential discontinuities. The orientation of the discontinuity surfaces of the 26 possible shocks shows a preference to be aligned somewhere between a direction perpendicular to the sun-earth line and a direction tangent to the local spiral angle of the magnetic field. It was possible to associate solar flares with 14 of the 26 possible shock events. Of these 14, a reliable orientation was deduced for 8 events. By considering the orientation of these 8 events in relation to the position of the parent flares on the solar disk it is suggested that a typical shock front propagating out from the sun has a radius of curvature less than but of the order of 1 AU.

“The human being as he is put together, can, for the purposes of talking about him, be divided into two major parts: his intellect, and his sensibility. We are accustomed to thinking of persons as divided into segments, and I propose to speak abouthe person in his intellectual capacity and in his capacity for sensibility.”With these words, one of America's distinguished scholars, Harold Taylor, began his address at a general session of the MENC Philadelphia convention in March. In his speech, which begins as an article on the next page, he first commented about the point of view from which he spoke; second, he commented on current education; and third, he presented particular examples of what he means by …

Histochemical and ultrastructural consequences of pH variations in growth media were studied using three normal human fibroblast strains. Histochemical staining for acid phosphatase indicated increased amounts of enzyme activity in cells grown at higher pH. The ultrastructural consequences of an increase in growth medium pH was dramatic. A picture resembling storage disease developed in these cells within a few days. The cells became filled with bodies which could roughly be divided into two types. Type I had a homogeneous matrix, stained slightly with ruthenium red, was usually not membrane bound, and exhibited no acid glycerophosphatase activity. The nature and origin of these bodies is unclear. Type II bodies contained whorles of membranes and inhomogeneous matrix which was acid phosphatase positive but did not stain with ruthenium red. This type was always membrane bound and qualifies as lysosomes. Normal cells thus grown at higher pH were morphologically similar to cells cultured at neutral pH from patients with I-cell disease. These morphologic changes did not affect cell viability or cell growth.

Extract: Histochemical and ultrastructural consequences of pH variations in growth media were studied using three normal human fibroblast strains. Histochemical staining for acid phosphatase indicated increased amounts of enzyme activity in cells grown at higher pH. The ultrastructural consequences of an increase in growth medium pH was dramatic. A picture resembling storage disease developed in these cells within a few days. The cells became filled with bodies which could roughly be divided into two types. Type I had a homogeneous matrix, stained slightly with ruthenium red, was usually not membrane bound, and exhibited no acid glycerophosphatase activity. The nature and origin of these bodies is unclear. Type II bodies contained whorles of membranes and inhomogeneous matrix which was acid phosphatase positive but did not stain with ruthenium red. This type was always membrane bound and qualifies as lysosomes. Normal cells thus grown at higher pH were morphologically similar to cells cultured at neutral pH from patients with I-cell disease. These morphologic changes did not affect cell viability or cell growth.Speculation: A morphologic picture of severe storage disease can be induced in normal fibroblasts simply by increasing the medium pH. This is in agreement with our earlier observation that the lysosomal function of mucopolysaccharide degradation is progressively inhibited as pH of the growth medium increases. When attempting to diagnose genetic disease in cultured cells it is important to realize that intracellular lysosomal function is sensitive to extracellular pH. The observation of such pH sensitivity might also be a useful tool in studies on the general nature of lysosomal function.

Certain antihuman lymphocyte sera raised by immunization of horses with whole thymus homogenate contain antiglomerular basement membrane (GBM) antibody and cause severe glomerulonephritis in nonhuman primates. This study was done to characterize this antibody and attempt its removal with isolated human GBM. Injection of radiolabeled antilymphocyte globulin (ALG) into rats revealed that 0.9 bound to kidney, 0.3 to liver, and 0.1 to spleen. Immunofluorescence studies showed antibody bound to the GBM in the kidney, around central veins and along sinusoids in the liver, and along sinusoids in the spleen. There was no uptake by the thymus. Use of a species with larger renal mass did not increase the percentage of antibody bound to kidney (KFAb). In contrast to in vivo studies, 5 of radiolabeled ALG was bound by GBM in vitro. When ALG was absorbed with human GBM, it no longer bound to kidney in vivo, as detected by immunofluorescence, and the KFAb content was reduced to less than 0.005. However, its lymphocytotoxicity was retained. The results show that the anti-GBM antibody in this ALG has broad connective tissue specificity, is readily absorbed by GBM in vitro, and probably arose in response to connective tissue in the thymus homogenate used for immunization.

Extract: Four patients with the clinical findings of mucolipidosis III were studied. Cultured skin fibroblast cells from three of these four patients were low in each of the five lysosomal enzyme activities measured. The ranges of the enzyme activities in these three patients were as follows: N-acetyl-ß-glucosaminidase (11–19% of normal), ß-galactosidase (26–33% of normal), a-fucosidase (31–55% of normal), a-mannosidase (53–62% of normal), and arylsulfatase A (16–21% of normal).In contrast, marked increases in the same enzyme activities were found in serum samples from the same patients. These include N-acetyl-ß-glucosaminidase (7–16 times normal), ß-galactosidase (8–11 times normal), a-fucosidase (5–10 times normal) and arylsulfatase A (14–24 times normal). Similar increases in the enzyme activities were also found in serum of patient 1; however, the changes were less dramatic.An electrophoretic analysis of one of these enzymes (N-acetyl-ß-glucosaminidase) revealed an abnormal pattern in the cultured fibroblast extracts; however, the presence of a normal pattern in the serum samples suggests that this is not due to an alteration in the primary amino acid sequence.Speculation: The lysosomal enzyme activities in serum and fibroblast extracts from the mucolipidosis III patients reported here are very similar to those found previously in mucolipidosis II (I-cell) patients. This suggests that the nature of the defect may be very similar in these two distinct disorders.

Early in the present century Professor Norman Kemp Smith developed the idea that the “establishment of a purely naturalistic conception of human nature by the thorough subordination of reason to feeling and instinct, is the determining factor of Hume's philosophy.” Since then several more studies of Hume have revealed a growing emphasis on positive elements in his naturalism, in correction of the traditional view of Hume as primarily a phenomenalist and self-defeating sceptic.

Prenatal exposure to oral anticoagulants during pregnancy may result in defective fetal development or life-threatening hemorrhage. Fetal exposure during the first eight weeks of pregnancy may cause abnormal development of the facial structures, hypoplastic digits, stippled epiphyses, and mental retardation. Midtrimester exposure may result in optic atrophy, faulty brain growth, and developmental retardation. Third-trimester exposure may produce fetal anticoagulation, predisposing the infant to life-threatening hemorrhage in the perinatal period. Anticoagulation with heparin sodium does not provide a clearly safe alternative, since this therapy has been associated with excessive fetal loss.(JAMA 243:1549-1551, 1980)

THE N-acetyl-β-D-glucosaminidase (hexosaminidase) activity in cultured human fibroblasts consists of at least three components (A, B and C)1–3. At least two of these (designated Hex A and Hex B) seem to be closely related, for (1) antiserum against Hex A reacts against Hex B, and vice versa4,5(2) in Tay-Sachs disease only Hex A activity is deficient, accompanied by an increase in Hex B activity in certain tissues1,6, and (3) both Hex A and Hex B activities are missing in Sandhoff disease, another autosomal recessive disorder7. But in spite of several theories8–11, the precise relationship between these components remains unknown, as does the nature of the genetic and biochemical relationships between the two diseases. To investigate these questions we have fused Tay-Sachs with Sandhoff fibroblasts and obtained cultures containing heterokaryons which produce a hexosaminidase which is absent from the parent lines. It has the electrophoretic and heat lability characteristics of the Hex A found in normal fibroblasts.

Summary: The establishment of cultured cell lines from skin biopsies stored at −196C for periods up to 1 year has been investigated. Attempts to initiate cell cultures from the frozen tissue samples were uniformly successful. There was no alteration in chromosome constitution, morphological appearance, or specific activities of lysosomal enzymes in cells cultured from the stored samples. This process can safeguard against failure of the initial tissue culture and provide an alternate means of storing viable cells when it is impossible or impractical to initiate a cell culture immediately.

Several methods were tested for the nondestructive separation of tannins from other plant constituents which might have antitumor activity. A comparison was made of precipitation of tannins by caffeine or lead acetate and chromatography on polyamide. The caffeine procedure was preferred over lead acetate; both tannins and nontannins were effectively separated and the caffeine conveniently removed. Polyamide was an effective tannin remover; nontannins were easily collected but tannins were irreversibly adsorbed. The application of the caffeine procedure to a variety of plants is described.

No abstract.