Identification of small molecular compounds and fabrication of its aqueous solution by laser-ablation, expanding primordial cartilage.

OBJECTIVE: The discovery of small molecular compounds that expand cartilage is needed. We searched for small molecular compounds that expand cartilage or enhance the actions of bone morphogenetic proteins (BMPs) on cartilage. DESIGN: Metatarsal primordial cartilage explants prepared from 14.5 days postcoitum (d.p.c.) mouse embryos were organ-cultured in the presence or absence of BMPs and/or 4-(5-Benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H-imidazol-2-yl)-benzamide hydrate (BPIB) and its related molecules. The perichondrium was removed from some of the cartilage explants by partial digestion with collagenase. BPIB aqueous solution was prepared by fragmenting BPIB crystals in water with laser irradiation and then added to cartilage explants in organ culture. RESULTS: We found that small molecular compounds, BPIB, available as SB431542 from Sigma and its related molecules, expand primordial cartilage explants in organ culture. These molecules are transforming growth factor-ß (TGF-ß) inhibitors, and the addition of excess TGF-ß reduced cartilage expansion induced by these molecules. The co-administration of BPIB and BMPs synergistically expanded cartilage explants. Removal of the perichondrium abolished BIPB-induced cartilage expansion but not BMP-induced cartilage-expansion, suggesting that BPIB, but not BMPs, expands cartilage through the perichondrium. Furthermore, we used the laser-ablation technique to generate BPIB aqueous solution in the presence of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) without the use of hazardous dimethyl sulfoxide (DMSO). The laser-ablation-generated BPIB aqueous solution was more stable, expanded cartilage explants more effectively than BPIB colloidal solution prepared with DMSO, and synergistically enhanced BMP-induced cartilage expansion. CONCLUSIONS: A small molecular compound, BPIB, expands primordial cartilage explants. A BPIB aqueous solution was created by laser-ablation without using DMSO and proved to be biologically active.

Combat-injured service members and their families: the relationship of child distress and spouse-perceived family distress and disruption.

Combat injury in military service members affects both child and family functioning. This preliminary study examined the relationship of child distress postinjury to preinjury deployment-related family distress, injury severity, and family disruption postinjury. Child distress postinjury was assessed by reports from 41 spouses of combat-injured service members who had been hospitalized at two military tertiary care treatment centers. Families with high preinjury deployment-related family distress and high family disruption postinjury were more likely to report high child distress postinjury. Spouse-reported injury severity was unrelated to child distress. Findings suggest that early identification and intervention with combat-injured families experiencing distress and disruption may be warranted to support family and child health, regardless of injury severity.

Military families and children during operation Iraqi freedom.

The general public has become increasingly interested in the health and well being of the children and families of military service members as the war in Iraq continues. Observers recognize the potential stresses or traumas that this population might undergo as a result of the military deployment or the possible injury or death of military family members. While such concern is welcomed, it is sometimes misplaced. Not infrequently, conclusions that are drawn are fraught with misunderstanding and bias based upon lack of understanding of the military community or a preconceived notion of the vulnerabilities of the population. This problem is compounded by the paucity of scientific study. In this article the authors review the strengths of military families as well as the unique challenges that they face. The authors also highlight parental deployment, parental injury and parental death as unique stresses to military children and families. Available and pertinent scientific information is reviewed. Clinical observations of children and families during the ongoing war in Iraq are presented.

Relationship between fat distribution and lipid and apolipoprotein profiles in young teenagers.

The influence of obesity and fat distribution on serum levels of lipoprotein and apolipoprotein was investigated in 294 Japanese junior high school children (12-13 years of age). Serum levels of low-density lipoprotein cholesterol (LDLC) (P = 0.013), triglycerides (TG) (P = 0.0006), and apolipoprotein B (apoB) (P = 0.003), and the apoB/A-I ratio (P = 0.005) were significantly higher and serum levels of high-density lipoprotein cholesterol (HDLC) (P = 0.00003) and apoA-1(P = 0.003) were significantly lower in obese boys than in non-obese boys. The serum levels of TG (P = 0.013) and the apoB/A-I ratio (P = 0.011) were significantly higher and the serum levels of HDLC (P = 0.004) was significantly lower in obese girls than in non-obese girls. The LDLC/apoB ratio was lower in obese girls than in non-obese girls (P = 0.03). Obesity (> or = 20% of ideal weight) was strongly correlated with the serum levels of lipids and apolipoproteins in boys; this relationship was less clear in girls. The degree of obesity and the body mass index (BMI) were more strongly correlated with serum levels of lipids and apolipoproteins in boys than in girls. In boys, atherogenic lipoproteins and apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the thickness of the triceps skinfold, while in girls the anti-atherogenic lipoproteins and apolipoproteins, such as HDLC and apoA-I, showed a stronger correlation with both the triceps and the subscapular skinfold thicknesses. In girls the relationships between the BMI and the degree of obesity and the thickness of the subscapular skinfold (S) thickness were similar to the relationships between those parameters and the triceps skinfold (T) thickness. In boys, these parameters showed a stronger correlation with the subscapular skinfold thickness than with the triceps skinfold thickness. The correlation coefficients for the relationships between skinfold thickness and lipid and apolipoprotein levels were similar to the coefficients for the relationships between skinfold thicknesses and the severity of obesity and the BMI. The distribution of central-type fat accumulation, which is indicated by the thickness of the subscapular skinfold, the S/T ratio and S-T value, was inversely correlated with the HDLC level in both boys and girls. The degree of obesity was strongly correlated with the atherogenic lipoprotein profile in boys, in part because the subscapular skinfold thickness was strongly correlated with the degree of obesity and the BMI. In girls, the correlations between indices of central-type obesity and atherogenic lipid and apolipoprotein profiles were stronger than in boys. These data suggest that childhood obesity may be an early cardiovascular risk factor.

Treatment of aplastic anemia with antithymocyte globulin, cyclosporin A, methylprednisolone, danazol and recombinant human granulocyte-colony stimulating factor.

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 x 10(9)/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17-53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.

Epidermal nevus syndrome with hemimegalencephaly: neuropathological study.

A neuropathologic examination of a 5-year-boy with epidermal nevus syndrome and hemimegalencephaly revealed 1) left hemimegalencephaly with an increased volume of the white matter, and 2) cerebral polymicrogyria with pachygyria, heterotopic neurons and prominent astrogliosis. Golgi staining revealed hypertrophic neurons with increased dendrites and spines. The hemihypertrophy of the cerebral hemispheres seems to have contributed to an increased volume of the white matter with migration disorder, and may have been due to a disorder in the germinal cell proliferation stage.

Epidermal nevus syndrome with hemimegalencephaly: a clinical report of a case with acanthosis nigricans-like nevi on the face and neck, hemimegalencephaly, and hemihypertrophy of the body.

A 5-year-old boy with the epidermal nevus syndrome and hemimegalencephaly is reported. He had pigmented nevi on the forehead and neck, and hemihypertrophy of the body from the birth. He developed intractable seizures, mental retardation, and right hemiparesis. His seizure pattern changed from early infantile epileptic encephalopathy to infantile spasms at 2 months of age. Electroencephalograms showed a suppression-burst pattern in the neonatal period, subsequently changing to hypsarrhythmia. Computerized tomography of the brain disclosed slight dilatation of the posterior horn of the lateral ventricle at the age of 2 months. Later, hemimegalencephaly with calcification on the left side of the brain was noted. Histological examination of the pigmented nevus on the neck showed it to be an acanthosis nigricans-like lesion. Clinical differences between tuberous sclerosis and epidermal nevus syndrome with hemimegalencephaly are discussed.

[Evaluation of fosfomycin in Campylobacter jejuni enteritis].

Out of 1,219 pediatric patients who were brought to our hospital with chief complaint of diarrhea and abdominal pain and in whom stool cultures were obtained for bacteriological studies in the 17 month period from May 1 in 1981 to September 30 in 1982, Campylobacter jejuni was isolated in 203 patients (16.7%). In this study we assessed the efficacy of fosfomycin (FOM) for C. jejuni enteritis. Results of antibiotic susceptibility tests revealed that C. jejuni is highly sensitive to FOM. The efficacy of FOM was confirmed both clinically and bacteriologically. Moreover, improvement in diarrheal symptoms and the duration required for cultural conversion under FOM treatment were assessed. From the results obtained, it was considered that FOM is an antibiotic with high efficacy for the treatment of C. jejuni enteritis.