Synthesis of bovine growth hormone by Streptomyces lividans.

Streptomyces lividans 66 was transformed with a plasmid containing the regulatory region of the Streptomyces fradiae aph gene and a structural gene that specifies bovine growth hormone (bGH). When grown in liquid culture the transformant contained a protein identical to authentic bGH, as judged by radioimmunoassay and immuno-blotting (Western analysis). The bGH was present in cells that had been in culture for up to four weeks but was not found in the medium. The strategy employed should be generally applicable to the expression of foreign genes in actinomycetes.

Penfluridol: an open phase III study in acute newly admitted hospitalized schizophrenic patients.

An open study was carried out in 17 acutely ill, newly admitted, floridly psychotic schizophrenic patients to a city hospital in New York. Penfluridol was given on a daily basis up to doses of 120 mg and patients were rated objectively by means of different psychometric evaluations; vital signs were monitored daily as were side effects. The drug was found to be a rapid acting, well-tolerated, and highly effective antipsychotic agent within the population of patients explored and within the dose range used. It was particularly effective in acutely agitated floridly paranoid schizophrenics; a statistically significant impact was achieved by 7 days and usually within 72 h after initiating treatment. The drug appears unique in that (1) its effects are realized without the untoward and usually troublesome effects of nonspecific sedation attendant upon the use of many other 'neuroleptic' medications, and (2) even within the relatively high doses used it produced no hypotensive effects. It is concluded that this appears to be a unique antipsychotic agent and a potentially important addition to the treatment armamentarium of both acute and chronic schizophrenic individuals.

Prognostic factors in breast cancer--a pathological and immunological study of patients with stage 1 breast cancer.

In order to analyze which features determine a poorer prognosis we undertook a study of 91 consecutive patients with pathological Stage I breast cancer operated on at Beth Israel Medical Center (1968-71). Tumor tissue slides were reviewed and features such as: tumor size, histologic type, nuclear grade, lymphocytic and perivenular lymphocytic infiltration, as well as sinus histiocytosis in the lymph nodes removed. Records were reviewed and classified according to age and ethnic background. Survival and recurrence data were recorded up to 14 years post-mastectomy. Also determined was the presence of an antigen, previously detected in certain human breast cancer tumor tissues, which has been found to cross-react immunologically with the 52,000 dalton major envelope protein of the mouse mammary tumor virus (MMTV--gp52). Ten-year cumulative disease-free survival was 0.65. Univariate analysis of survival within various factors revealed that the only statistically significant influencing factor was the presence or absence of the antigen. Factors such as perivenous lymphocytic infiltration, diffuse lymphoid infiltration and sinus histiocytosis in regional lymph nodes also showed trends in favor of improved survival but the sample may be too small for statistical significance. The presence or absence of the antigen was independent of the host immunological reaction. There was no relationship between localization of tumor, whether medial or lateral and survival, nor with presence or absence of antigen.

A complicated stress fracture of the femoral neck--a case report.

A case is presented of a stress fracture of the femoral neck complicated by complete fracture. Additional complications arose when the repaired fracture went on to non-union due to bending of the DHS screw, requiring revision surgery with a valgus osteotomy. The case is important because this type of stress fracture has previously been considered to be safe from risk of complete fracture. The failure of the operative treatment has implications for young patients treated similarly.

[Pierre Robin sequence: postoperative complications following cleft palate surgery. A retrospective study covering 25 years]. / Pierre-Robin-Sequenz -- postoperative Komplikationen nach Gaumenspaltverschluss. Eine retrospektive Studie über 25 Jahre.

BACKGROUND: In a 25-year retrospective review of 1976-2000, the postoperative course after cleft palate surgery and pharyngeal flap surgery in 87 children with Pierre Robin sequence was studied. PATIENTS AND METHODS: The study comprised 114 interventions with 87 primary palatoplasties; 17 patients required palatal fistulae repair and 10 children were treated with secondary pharyngoplasty procedures. All children were divided into three postnatal risk groups according to the severity of their symptoms at birth and in the course of the early months of life. RESULTS: A direct correlation was seen between the incidence of early postnatal difficulties and the postoperative obstructive complications after cleft palate surgery and pharyngeal flap surgery. Thus, children experiencing obstructive problems at birth (high postnatal risk group) displayed more severe complications at the time after cleft palate repair. In children undergoing pharyngeal flap surgery not only early postoperative obstruction but also late obstructive sleep apnea can occur.

Breast cancer in Israel. Histopathologic types in the different population groups.

The histological sections of 1,605 cases of breast cancer in Israeli women were examined to determine the frequency of the various histological subtypes inthe different population groups. Infiltrating ductal carcinoma was the most common type in all groups. Circumscribed and medullary carcinoma were relatively less frequent among women born in North Africa than among immigrants from Europe or Asia. Invasive lobular carcinoma was very rare among women born in Asia. The findings are compared with those in other countries and discussed in relation to survival patterns in the different population groups in Israel.

Specific cleavage of the p15A primer precursor by ribonuclease H at the origin of DNA replication.

We report studies on the mechanism of initiation of DNA replication by p15A, a small plasmid whose origin of replication is known to function much as does that of ColE1. Previous work has shown that an RNA primer for DNA synthesis is generated by the action of RNase H (EC 3.1.26.4) on a precursor transcript. The precursor initiates well upstream of the origin of replication and somehow forms a hybrid with its template during transcription. Here we show that when RNase H cleaves the hybrid at 0 degrees C, an additional cleavage product besides the primer can be identified. Using two-dimensional RNA sequencing techniques, we have established the sequence of this product to within a few nucleotides of each end. The position of the 5' end indicates that the nuclease introduces a nick or very small gap in the precursor at the origin. This suggests that some sequence or structure directs the enzyme to the origin. The position of its 3' end indicates that the precursor terminates at or near a series of six dAs in the template strand about 190 nucleotides from the origin of replication. The data indicate that hybrid formation may be necessary for termination of the precursor at this downstream site.

Immunohistochemistry of primary gastrointestinal lymphomas: a study of 76 cases.

A retrospective study of 76 primary gastrointestinal lymphomas utilizing an avidin: biotinylated horseradish peroxidase complex (ABC) technique demonstrated 22 B-cell lymphomas, including two associated with alpha-heavy chain disease. Seven cases were classified as true histiocytic lymphomas based on a positive reaction for one or more of three histiocytic enzyme markers utilized, predominantly alpha-1-antitrypsin and alpha-1-antichymotrypsin. However, in 20 cases, an intense admixture of reactive histiocytes was noted and these cells stained preferentially for the enzyme, lysozyme. Twenty cases, which stained for both kappa and lambda light chains and positively or negatively for albumin, could not be classified and 27 cases failed to stain with any of the antisera utilized.

Mapping 5' termini of JC virus early RNAs.

Within its enhancer promoter region, the MAD-1 strain of JC virus (JCV) has two 98-base-pair tandem repeats, each containing a TATA box-like sequence. In the present study, polyadenylated early JCV mRNAs were isolated 5 or 29 days after infection of primary human fetal glial (PHFG) cells. By using S1 nuclease, the 5' termini of the early mRNAs were mapped to nucleotide position(s) (np) 122 through 125, which lies within an AT rich region (at np 113 through 127). In contrast, when JCV DNA was transcribed in vitro, we observed a single major cluster of 5' start sites at np 94 through 97, which is approximately 25 base pairs downstream from one of the TATA boxes. By day 5, the earliest time at which JCV RNA was detected, viral DNA replication had begun; it continued for at least an additional 20 days. Since more late than early RNA was present at 5 days postinfection, the early RNAs whose synthesis began at np 122 through 125 may be analogous to SV40 late early mRNA (Ghosh and Lebowitz, J. Virol. 40:224-240, 1981). However, we have not detected RNAs with 5' termini 25 to 30 bp downstream from the TATA box at earlier times. While JCV contains two identical TATA boxes, one in each of the 98-bp repeats, only the upstream TATA box functions as an early promoter element.

Transformation of chronic lymphocytic leukemia to plasmacytoma.

In a woman with chronic lymphocytic leukemia (CLL), a maxillary plasmacytoma developed after 8 years. The membrane-bound immunoglobulin of the leukemic lymphocytes, the cytoplasmic immunoglobulin of the plasma cells, the serum monoclonal protein and the urine Bence-Jones protein had the same heavy and light chains--mu kappa. This suggests that the leukemic cells transformed to plasma cells. This very rare event is a complete reversal of the more common transformation that occurs in CLL and manifested by de-differentiation. Only in one case out of the 20 previously reported patients with CLL and multiple myeloma there was evidence, like in the current case, of a common clonal origin of the two B-cell neoplasms.

Extramedullary hematopoiesis with multiple tumor-simulating mediastinal masses in a patient with beta-thalassemia intermedia.

A patient with beta-thalassemia intermedia with massive extramedullary hematopoiesis in the mediastinum is presented. These masses, which simulate tumors, are usually asymptomatic only rarely causing spinal cord compression. The histologic examination showed that they consist of hematopoietic tissue. The importance of correct diagnosis without surgery is stressed.

Primary malignant tumors of the thyroid gland: a clinicopathologic study of 254 cases.

Of 254 primary malignant tumors of the thyroid gland diagnosed in the pathology department of the University of Cape Town, 212 (83.5%) were differentiated carcinomas. In this differentiated group, tumors composed exclusively of papillary structures exhibited the most favorable prognosis; local recurrences and/or spread were noted in tumors with a mixed papillary and follicular pattern and, more commonly association with 21 tumors (8.3%) but an associated multinodular goitre was found in only nine patients (3.5%). In addition to the well-known preponderance of thyroid carcinoma in women, a majority of lesions occurred in white patients in this series despite a higher hospital admission rate for coloreds (mulattos).

Construction and properties of recombinant plasmids containing the rII genes of bacteriophage T4.

The EcoRI digestion products of phage T4 DNA have been examined using a phage DNA transformation assay. A 2.6 X 10(6) Dalton fragment was found to contain the rII genes. This fragment was purified and then treated with HindIII endonuclease. The cleavage products were ligated to the vector plasmid pBR313 and viable recombinant plasmids recovered. A genetic assay was employed to demonstrate that the recombinants contained T4 DNA and to localize on the phage genetic map the EcoRI and HindIII sites cleaved during the construction of the plasmids. Preliminary characterization suggests that a fragment covering the beginning of the rIIA gene possibly contains a promotor which is active in uninfected cells.