Kinji Yokomori

Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors

The hSNF5/INI1 gene, which encodes a subunit of the SWI/SNF family of chromatin‐remodeling complexes and is located at 22q11.2, has been reported as a tumor suppressor gene inactivated in malignant rhabdoid tumors (MRTs). We analyzed this gene in varieties of pediatric solid tumors including MRTs, using the reverse transcription‐polymerase chain reaction (PCR) and PCR‐single strand conformation polymorphism method. We found 5 homozygous deletions, 2 truncated mutations, one missense mutation, and one silent mutation of the hSNF5/INI1 gene in 7 MRT cell lines, and one homozygous deletion, one microdeletion, one splicing acceptor site mutation, and one absence of expression in 7 fresh tumor tissues of MRT and atypical teratoid (AT)/rhabdoid tumors (RTs). Homozygous deletions were also found in one (KYM‐1) of 8 rhabdomyosarcoma (RMS) cell lines. To investigate characteristics of the KYM‐1 cell line, we have established KYM‐1 tumors in nude mice into which KYM‐1 cells were transplanted. Notably, we found that MyoD1, known as a marker for RMS, was not expressed in the KYM‐1 cell line as well as MRT cell lines and fresh tumors. Histopathologic, cytogenetic, and molecular studies of the KYM‐1 cell line and KYM‐1 tumors in nude mice have revealed that this RMS cell line should be MRT rather than RMS. RMS‐carrying aberrations of the hSNF5/INI1 gene should be reevaluated. No aberrations of this gene were found in the other 34 cell lines or 80 fresh tumor specimens except the single nucleotide polymorphisms in the 3′ noncoding region. These results suggest that alterations of the hSNF5/INI1 gene were restricted to MRTs or AT/RTs in pediatric solid tumors.

A novel immunoassay of smooth muscle myosin heavy chain in serum

We have developed a double monoclonal sandwich enzyme immunoassay to measure smooth muscle myosin heavy chain (MHC). Analytical performance of the assay showed reliable detection of smooth muscle MHC in human sera. The mean of the smooth muscle MHC level in normal human sera was 0.9 +/- 0.9 ng/ml. In sera of patients with aortic dissection, the smooth muscle MHC level sharply elevated at the onset and rapidly decreased to normal levels. Immunoassay of smooth muscle MHC in serum is a promising method for biochemical diagnosis of smooth muscle disorders.

Internal jugular phlebectasia in two siblings: Manometric and histopathologic studies of the pathogenesis

Two brothers, 4 years and 6 years of age, presented with a swelling in the right side of the neck. Ultrasonography and venography confirmed a diagnosis of phlebectasia of the right internal jugular vein (IJV). In an attempt to elucidate the etiology of this rare lesion, venous pressures in both the dilated right IJV and in the left IJV were taken under general anesthesia with intratracheal intubation at the time of surgery in each patient. No significant difference in pressure elevation with increase of intrathoracic pressure by overinflating the breathing bag was observed between the right and left IJV, suggesting that there would be no mechanical obstructive process generated on exertion, in each case. Microscopic examinations of a dissected portion of the dilated IJV showed paucity of muscle layer of the vein wall in the younger patient, and absence of that in the elder. Therefore, we assume that congenital muscle defect of the right IJV wall, rather than mechanical obstruction in the lower neck or the mediastinum, might cause phlebectasia. To our knowledge, this is the first report of IJV phlebectasia in siblings.

Advantages and pitfalls of amnion inversion repair for the treatment of large unruptured omphalocele: Results of 22 cases☆

This is a report of our experience with 22 cases of large unruptured omphaloceles treated by amnion inversion during the period 1973 through 1990. The method is characterized by three stages: (1) a silastic sheet is sutured directly to the skin around the amniotic membrane, under local anaesthesia, without dissection between the skin and the amnion; (2) the reduction of herniated viscera into the abdominal cavity is achieved by squeezing the sheeting using a specially modified stapler; and (3) the amniotic membrane is preserved intact, and inverted into the abdominal cavity at the time of abdominal wall closure. Of the 22 infants, 19 survived with satisfactory results. Two patients died of multiple associated anomalies, and the remaining patient died of sepsis arising at the time of the final abdominal closure. This procedure has proved to be effective and safe for high-risk patients with congenital heart diseases, anal atresia, tracheoesophageal fistula, or bronchial stenosis and prematurity. The practical aspects of the procedure, as well as its advantages and pitfalls, are illustrated.

Alpha-fetoprotein, prealbumin, albumin, alpha-l-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors

According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.

Hirschsprung's disease associated with Ondine's curse: A special subgroup?

The authors report a case of the rare occurrence of congenital central hypoventilation syndrome (Ondines curse) and long segmental colonic aganglionosis (Hirschsprungs disease). A review of 24 reported cases showed that the proportion of females having this concurrence is higher than for ordinary Hirschsprungs disease. It also appears that the aganglionic segment is much longer in these cases than in ordinary Hirschsprungs disease.

Complete disappearance of unresectable hepatoblastoma by continuous infusion therapy through hepatic artery.

A 4-month-old infant with a huge unresectable hepatoblastoma was treated by continuous infusion therapy with 5-fluorouracil, vincristine, Adriamycin, and cisplatin, through the hepatic artery. Following 18 months of chemotherapy, the tumor disappeared completely and the initially sky-high serum alpha-fetoprotein levels returned to normal. At the time of this report, the patient continues to do well without tumor recurrence 6 years following discontinuation of the combination chemotherapy.

Tyrosine hydroxylase and choline acetyltransferase activity in human neuroblastoma correlations with clinical features

Two neurotransmitter‐synthesizing enzymes, tyrosine hydroxylase (TH) and choline acetyltransferase (CAT), were assayed in neuroblastoma tissues from 24 children, in human neuroblastoma tissues serially transplanted in nude mice, and in human neuroblastoma cells in culture. Among tissues from 24 children, five showed an adrenergic pattern with significant TH activity alone, seven showed a cholinergic pattern with significant CAT activity alone, and the remaining 12 specimens showed a “both‐active” pattern with both TH and CAT activity. Enzymatic activities were maintained through many serial passages in vitro and in nude mice. All four specimens from children under one year of age exhibited the adrenergic pattern. In general, enzymatic activity was not correlated with degree of differentiation histologically. Among four cases of paravertebral dumb‐bell type in this series, two were cholinergic, one was adrenergic, and the last was both‐active. These results suggest that dumb‐bell type tumors may arise from either sympathetic ganglia or dorsal root ganglia. This study supports the concept that neuroblastomas are a composite of adrenergic and cholinergic cells. Significant changes in the relative proportions of these two cell types were observed with time, and after extensive therapy. Different metastatic sites often exhibited important differences in enzymatic activity. These results help to account for clinical discrepancies between urinary VMA levels and tumor growth. Assays for TH and CAT can be useful for confirming a diagnosis of neuroblastoma, and have important potential for helping to clarify the natural history of neuroblastoma. Cancer 52:263‐272, 1983.

A new urinary mass screening system for neuroblastoma in infancy by use of monoclonal antibodies against VMA and HVA

As an assay system for mass screening of infants with neuroblastoma, a new method of determining urinary vanillylmandelic acid (VMA) and hemovanillic acid (HVA) levels--an enzyme immunoassay (EIA) method--was developed. By using two different monoclonal antibodies, one against VMA and the other against HVA, this system can assay 400 urine samples for both catecholamine metabolites in five hours. By measuring both VMA and HVA levels in 275 urine samples (62 from patients with neuroblastoma, 13 from patients with control tumors, 200 from healthy infants as controls) by the EIA method, as well as by high performance liquid chromatography (HPLC), we examined whether the EIA system is as accurate as the HPLC. There were significant correlations between values obtained by the two systems, both for VMA and for HVA, suggesting that the EIA method would be a more reliable and convenient system for mass screening of infantile neuroblastoma as compared with conventional qualitative tests with inevitable high false-positive rate.

Nude mouse xenograft study for treatment of neuroblastoma: Effects of chemotherapeutic agents and surgery on tumor growth and cell kinetics

Four human neuroblastomas transplanted into nude mice were used for experimental chemotherapy and surgery, and the following results were obtained. Cyclophosphamide was the most effective for human neuroblastoma, cis-platinum being the second, among several chemotherapeutic drugs examined. Aclacinomycin A is more effective than Adriamycin. VM26 should be administered 48 to 72 hours after injection of cis-platinum, according to flow cytometric analysis. Flow cytometric analysis also disclosed that residual tumor grows most rapidly seven days after subtotal excision. However, chemotherapy is more effective in the postoperative period than it is in the preoperative period.