Comparison of adult height between patients with XX and XY gonadal dysgenesis: support for a Y specific growth gene(s).

Adult height was compared between published cases of patients with XX gonadal dysgenesis (XXGD) and those with XY gonadal dysgenesis (XYGD). The mean adult height of XYGD patients (171.0 cm (SD 7.8), n = 27) was significantly greater than that of XXGD patients (164.4 cm (7.7), n = 27) (p less than 0.01). This finding supports the existence of a Y specific growth gene(s) which promotes statural growth independently of the effects of gonadal sex steroids.     

Method for In Situ Evaluation of Superoxide Production by Pulmonary Macrophages in the Rat

In order to investigate superoxide production by pulmonary macrophages in the rat, a route was created by ligating both the inferior and superior venae cavae and resecting the aorta after cannulation through the inferior vena cava into the right atrium of the heart. Lung perfusion was performed via this route with nitro blue tetrazolium. Although there was no formazan deposition throughout the lung, it became detectable in both alveolar and interstitial macrophages when phorbol myristate acetate was added to the perfusate. This deposition was markedly enhanced by previous injection of Corynebacterium parvum. The deposition disappeared after further addition of Cu(Lys)₂, a scavenger of superoxide anions. This procedure may be useful for estimating in situ the ability of pulmonary macrophages to produce superoxide in the rat.     

C to T transition at the first nucleotide of codon 63 of the β-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy

Summary Hemoglobin (Hb) M-Saskatoon, a variant of methemoglobin, is characterized by mild hemolysis. It is caused by the substitution of a histidine by a tyrosine at the 63rd amino acid residue of the -globin chain. Amplification and sequence analysis of genomic -globin DNA from an Indonesian boy diagnosed as having the more severe disease thalasemia demonstrated the presence of a C to T transition at nucleotide 473 in one of the two -blogin genes resulting in a histidine to tyrosine substitution at 63rd residue. This amino acid change matched with that reported in Hb M-Saskatoon. This nucleotide change abolished a recognition site for the restriction endonucleaseNlaIII.NalIII digestion of the corresponding -globin DNA amplified from the patient's parents indicated that the mutation was inherited through from his mother. This result shows that the world-wide distribution of Hb M-Saskatoon extends to Indonesia, where it was not previously identified. Possible causes of the unusually severe symptoms observed in the case are discussed.     

Mycobacterium avium-M. intracellulare binds to the integrin receptor alpha v beta 3 on human monocytes and monocyte-derived macrophages.

Mycobacterium avium-M. intracellulare is an intracellular pathogen responsible for the highest incidence of disseminated bacterial infection in patients with AIDS. Treatment of the infection is difficult and has been of limited efficacy. Attachment of the organism to macrophages is a critical early step in the establishment of the disease. In the present study, we isolated and identified a receptor that mediates attachment of M. avium-M. intracellulare to human peripheral blood monocytes and monocyte-derived macrophages. On Western blotting, (immunoblotting), the receptor was found to cross-react with antibodies against a human vitronectin receptor (alpha v beta 3). The receptor could be purified from monocyte extracts by using monoclonal antibodies (MAbs) against the alpha v subunit of vitronectin receptor coupled to CNBr-Sepharose 4B, as well as with the adhesive tripeptide sequence arginine-glycine-aspartic acid (RGD) coupled to CNBr-Sepharose 4B. Surface-bound MAbs directed against alpha v beta 3 were found to inhibit the attachment of M. avium-M. intracellulare to monocyte-derived macrophages in an in vitro inhibition assay, while MAbs directed against CD14, CD18, alpha 2 beta 1 and platelet glycoprotein gpIIb/IIIa receptors did not inhibit this attachment. These observations suggest that alpha v beta 3 on the surface of human monocytes and monocyte-derived macrophages may function as a receptor for M. avium-M. intracellulare. Identification of a receptor for M. avium-M. intracellulare on macrophages may offer new approaches to the prevention and control of M. avium-M. intracellulare infection at the cellular level.     

Site-specific growth of Nocardia asteroides in the murine brain.

The growth of Nocardia asteroides GUH-2 and two mutants (NG-49 and I-38-syn) in regions of the brains of BALB/c mice was determined by microdissection and viable counting. GUH-2 grew throughout the murine brain but at different growth rates that depended on the specific location. The rate of increase in total CFU per brain during GUH-2 infection was unaffected by the inoculum size; however, in five of eight brain regions, an alteration in the inoculum size resulted in altered nocardial growth rates. Mutant NG-49 showed a significantly slower rate of increase in total CFU per brain than did the parental strain, GUH-2, and significantly decreased growth rates in seven brain regions. Mutant I-38-syn showed a rate of increase in total CFU per brain similar to that of the parental strain; however, this mutant grew significantly faster in the cerebellum and pons-medulla. Growth appeared to be a necessary precursor to the cellular damage that resulted in the variety of neurological disorders observed in mice infected with N. asteroides GUH-2, because mutant NG-49 exhibited a decreased ability to grow in specific regions of the brain and did not induce signs of neurological damage. In contrast, mutant I-38-syn induced neurological signs in a larger percentage of the infected animals than did parental strain GUH-2 and grew better in certain regions of the brain than did the parental strain. Furthermore, there appeared to be a relationship between the growth of N. asteroides in the substantia nigra and the induction of an L-dopa-responsive head shake that was observed in some of the mice following a sublethal intravenous injection of N. asteroides GUH-2.     

Genitourinary phenotype in XX patients with distal 9p monosomy

Although testicular development has been shown to be variably impaired in XY patients with distal 9p monosomy, ovarian and other genitourinary phenotype has poorly been studied in XX patients monosomic for the distal 9p region. Thus, we studied a 13-month-old infant with 46,XX,der(9)t(9;10)(p23;p13) (case 1) and an 11-year-old girl with 46,XX,der(9)t(9;16)(p23;q22) (case 2). Case 1 had primary hypogonadism (basal serum follicle stimulating hormone [FSH], 40.0 mIU/mL; leteinizing hormone [LH], 1.2 mIU/mL; estradiol [E2], <10 pg/mL), whereas case 2 had age-appropriate pubertal development (breast, Tanner stage 4; pubic hair, Tanner stage 3; menarche 11.7 years of age) and hormone values (FSH, 7.3 mIU/mL; LH, 6.7 mIU/mL; E2, 47 pg/mL). In addition, case 1 had hypoplastic labia majora, short distance between the vaginal orifice and the anus, and five renal cysts, and case 2 had anal atresia, short distance between the vaginal orifice and the anus, bilateral hydronephrosis of grade 3 with probable ureteropelvic junction stenosis, and renal dysfunction (serum creatinine, 1.52 mg/dL; urea nitrogen, 34.5mg/dL). Fluorescence in situ hybridization analysis for five regions and microsatellite analysis for 10 loci on 9p confirmed hemizygosity for the distal 9p region with the breakpoints between IFNA and D9S285 in case 1 and between D9S168 and D9S286 in case 2. The results, in conjunction with the previous data in XX patients with molecularly defined distal 9p monosomy, are consistent with the presence of a gene(s) involved in the development of indifferent gonad or subsequent ovarian differentiation in a approximately 11 Mb region distal to D9S168. In addition, it is possible that a gene(s) for anoperineal and renal development also maps distal to D9S168 and that for external genital development maps distal to D9S285 at the position approximately 16 Mb from the 9p telomere.     

Ultrastructural analysis of attachment to and penetration of capillaries in the murine pons, midbrain, thalamus, and hypothalamus by Nocardia asteroides.

The attachment to and penetration of endothelial cells in the pons and midbrain (especially the substantia nigra) regions of the brains of BALB/c mice by log-phase Nocardia asteroides GUH-2 cells were determined by both scanning and transmission electron microscopic analysis. Within 15 min after exposure, the nocardiae attached to the surface of the endothelial cell membrane. This attachment occurred primarily at the growing tip of the nocardial filament, and the outermost layer of the nocardial cell wall had regions (electron-dense areas) that bound firmly to the cytoplasmic membrane of the host cell. There appeared to be specificity for this binding localized within the capillaries and arterioles because some regions had large numbers of bacteria bound, whereas adjacent areas had no bacterial cells. Nocardial filaments that attached by the apex induced a cuplike deformation of the endothelial cell membrane. This was followed by a rapid penetration of the endothelial cell so that within 25 min many of the bacteria were internalized within the host cell. These internalized bacteria remained within vesicles, and there was no ultrastructural evidence of damage to the nocardial cell during this process. Heat-killed GUH-2 cells still attached to endothelial surfaces (at a reduced frequency), but they did not penetrate into the endothelial cell. These data suggest that brain-invasive nocardiae possess both an adhesin for attachment to the membrane of endothelial cells and an invasion factor that promotes nocardial penetration of these cells.     

CLINICOPATHOLOGICAL STUDY ON SMALL RENAL CELL CARCINOMAS WITH METASTASES

Seven metastasizing small renal cell carcinomas smaller than 30 mm in the greatest diameter were clinicopathologically studied for a better understanding of their characteristic features as compared to those of small tumors without metastases. Grayish-white infiltrating tumors in gross appearance and alveolar or solid microscopic structure consisting of granular or spindle cells and of atypical nuclei were suggestive of having metastases. Two tumors which had positive reactions to the lower nephron markers such as SB A, PNA, and/or DBA were considered to be of lower nephron origin and displayed poor prognosis. ACTA PATHOL. JPN. 37: 947–954, 1987.     

Undifferentiated Carcinoma of the Parotid Gland in a 10-Month-old Child

Malignant salivary gland tumors in children are very rare. This report describes the autopsy of a child with parotid gland cancer. The patient, a 10 month old girl, was admitted to the Nagoya First Red Cross Hospital with facial nerve palsy. lncisional biopsy of a post-auricular tumor was performed, and undifferentiated carcinoma was diagnosed. The patient died 6 months later of respiratory failure due to pulmonary lymphangitis carcinomatosis. Light and electron microscopic and immunohistochemical examinations of the tumor tissue were performed. The tumor cells were arranged in a medullary, sheet-like manner. Keratinization or mucus lakes were not observed. PAS-alcian blue staining demonstrated intracytoplasmic mucus as granules, and also small intercellular droplets of mucus that might otherwise have been unnoticed. Ultrastructurally, some of the tumor cells had tonofilament-like keratin filaments, and also small hollow spaces bounded by microvilli and containing secretory particles. These were stained by antisera against CEA and keratin. These findings are suggestive of differentiation to mucoepider-moid carcinoma. We also review and discuss malignant salivary tumors of epithelial origin in children. Acta Pathol Jpn 40: 149–152, 1990.     

Twenty-six-Week carcinogenicity study of chloroform in CB6F1 rasH2-transgenic mice

The carcinogenic potential of chloroform was evaluated in a short-term carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg) male and female mice received doses of 140 mg/kg and 240 mg/kg, respectively. N-methyl-N-nitrosourea was administered to rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. In both the rasH2-Tg and non-Tg mice, there was no significant increase in the incidence of neoplastic lesions by chloroform treatment. The incidence of hepatocellular foci in the rasH2- and non-Tg females receiving 240 mg/kg was increased. Forestomach tumors and malignant tumors occurred in most of the rasH2-mice in the positive control group. Swelling or vacuolation of hepatocytes, a toxic change induced by chloroform, occurred in both the rasH2-Tg and non-Tg mice. It is concluded that chloroform, a putative human noncarcinogen, did not show evidence of carcinogenic potential in the present study using rasH2-Tg mice. This study suggests that the rasH2-Tg mouse model may not be appropriate for detecting nongenotoxic carcinogens. However, the sensitivity of rasH2-Tg mice to nongenotoxic carcinogens should be assessed with consideration of the results from the other ILSI-HESI project studies.