Dipeptide synthesis catalyzed by aminoacyl-tRNA synthetases from Bacillus stearothermophilus

A new approach to enzymatic peptide synthesis by using aminoacyl-tRNA synthetase (ARS) as a catalyst has been investigated. Four ARSs (AspRS, HisRS, LeuRS and TyrRS) have been purified from a thermophilic bacterium, Bacillus stearothermophilus. By using TyrRS as a catalyst, tyrosine and leucinamide were shown to be condensed in the presence of ATP to give tyrosylleucinamide. In this manner, all of the ARSs investigated catalyzed the peptide synthesis reactions. TyrRS did not have strict specificity for the amino acid derivatives used as substrates and even D-amino acids were incorporated into peptides fairly easily in this enzymatic reaction. Preparative scale synthesis of L-Tyr-L-LeuNH₂ was carried out and from this the scope and limitation of this new enzymatic reaction as a tool to the peptide synthesis has been described.     

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.     

Case Report: Interferon induced coma in Sheehan's syndrome

A 54-year-old woman who was being treated with 10 million units (mu) of natural interferon (IFN)-α per day for chronic active hepatitis C at a local clinic, developed coma on the fourth day of treatment. On admission to Yamagata University Hospital, she was still in a state of semicoma with severe hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration of electrolytes, her condition improved remarkably. Endocrinological loading tests showed a hypofunction of the anterior pituitary gland. In consideration of these results, and her past experiences of haemorrhage during childbirth and subsequent amenorrhoea, we diagnosed her illness as a coma as a result of Sheehan's syndrome which had become overt during IFN therapy. She recovered completely after treatment with hydrocortisone and 1-thyroxine.     

Histological findings in asymptomatic hepatitis C virus carriers

There is controversy about clinical management of individuals who persistently have hepatitis C virus antibodies (HCVAb) but who have no symptoms or signs of liver disease. Liver biopsy samples were taken from 15 individuals, all of whom had normal alanine aminotransferase (ALT) levels, to determine the prevalence of liver disease and whether HCVAb and HCV-RNA correlate with histological findings. Eleven patients with hepatitis C viremia had histological evidence of chronic hepatitis on biopsy. On the other hand, four HCV-RNA-negative individuals had almost normal liver histology. These findings indicate that serum HCV-RNA is a sensitive and specific marker of liver disease in HCVAb-positive subjects, independent of ALT levels. Furthermore, these results suggest that there are very few histologically healthy carriers of HCV among HCV-RNA-positive individuals.     

Prognostic Significance of Extranodal Cancer Invasion of Mediastinal Lymph Nodes in Lung Cancer

The presence of perinodal cancer invasion in specimens obtainedfrom the mediastinum during curative surgery on 49 patientswith metastasis-bearing mediastinal nodes was determined andevaluated with special reference to its prognostic significance. When an en-bloc dissection technique for the mediastinal lymphnodes and fatty tissue surrounding the nodes during surgerywas used, lymphatic vessel invasion in fatty tissue other thana breach in the capsule of a lymph node by cancer could be seen.A breach in the node capsule and lymphatic vessel invasion aredesignated as "extranodal invasion" in this paper. A breach in the capsule was seen in 16 cases, lymphatic vesselinvasion in 12 and both a breach in the capsule and lymphaticvessel invasion in 4. In 17 cases there was only intranodalcancer metastasis. The 5-yr survival rate was 37.5% and 17.7%for patients with and without extranodal invasion, respectively.However, extranodal invasion did not seem to be a distinctiveprognostic factor.     

Local Recurrence after Sphincter-Saving Procedures for Carcinoma of the Rectum--An Analysis of 141 Cases--

During the past 18 years, 141 patients with rectal carcinomaunderwent curative sphincter-saving procedures. Local recurrencesoccurred in 17 patients, a recurrence rate of 12%. No significantcorrelation between the recurrence rate and the site of tumoror nodal involvement was found. Laparotomies were performedin 14 of the 17 patients with local recurrence. Thirteen patientsunderwent abdominoperineal excision. In five of them, the recurrentgrowths were completely resected, and they were thought to havedeveloped at the previously established suture line, while inthe remaining eight cases the operation was considered palliative.As the result of pathological study of these resected specimens,it is possible to draw the following conclusions:

1. The length of the distal margin of the normal bowel should bemore than 4 cm in locally advanced cases.
2. In patients whosesecond operation was not curative the recurrencesdid not developin the rectal stump or in the levator muscle,but in the pelvicwall.
3. Local recurrence after sphincter-saving procedures couldbeeffectively avoided by adequate clearance of the pararectalsoft tissues which could contain viable cancer cells, includingthe lymphatics and vessels as well as the lymph nodes.
4. Aftera sphincter-saving operation, the patient must be examinedundera strict follow-up regimen, because curative resectionof localrecurrent tumors by abdominoperineal excision willbe made possibleby earlier detection of the recurrence.

     

Long-term outcome of upper urinary tract carcinoma in situ: Effectiveness of nephroureterectomy versus bacillus Calmette-Guérin therapy

BACKGROUND: We examined the long-term outcome and compared the usefulness of nephroureterectomy with that of bacillus Calmette-Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS). METHODS: We retrospectively reviewed the post-treatment course of 17 patients with CIS of the upper urinary tract who had undergone either a nephroureterectomy (group A, n = 6) or BCG therapy (group B, n = 11) at our institute. RESULTS: Median follow up was 58.3 months (range 1-120 months). Four of the six patients in group A (67%) had no recurrence and remained cystoscopically, cytologically and radiographically free of disease. The cytology became negative after an 8-week course in nine of the eleven patients in group B (82%; eight of ten units, 77%). Two of the nine patients showed recurrence after BCG therapy. One patient died of respiratory failure caused by a side-effect of BCG, which was interstitial pneumonia. There was no significant difference in either the 5-year recurrence-free survival or the 5-year cancer-specific survival between groups A and B. CONCLUSIONS: BCG therapy for CIS of the upper urinary tract is as effective as nephroureterectomy in long-term outcome, although it has some dangerous aspects. Further experience with treatment of CIS of the upper urinary tract is required.     

An Inflammatory Polyp of the Sigmoid Colon Observed in a Case with a Ruptured Ovarian Dermoid Cyst

We present here a rare case, an ovarian dermoid cyst with fistulaformation into the sigmoid colon, which forms an inflammatorypolyp of the sigmoid colon. A 58-year-old woman was admitted because of occasional analbleeding. Several examination disclosed the elevation of erythrocytesedimentation rate, a positive test of stool specimen for occultblood, a polyp of the sigmoid colon in barium enema. Laparotomyshowed that a dermoid cyst of the left ovary had ruptured intothe sigmoid. The etiology of the rupture was "idiopathic." Thefistulous communication between the cyst and the sigmoid colonwas thought to have developed the inflammatory polyp over aperiod of about two years.