Biomedical subjects
Publications and source records attributed to R Herrmann.
Methotrexate and 5-FU were given sequentially with a 7-hour interval to 43 evaluable patients with heavily pretreated metastatic breast cancer. Partial remissions were seen in 12 patients (28%), indicating efficacy of this regimen in patients resistant to the conventional simultaneous application of these drugs.
The article reports on the findings obtained in 56 serial phlebographies of the upper extremity. Using 17 phlebographies without pathological findings as basis, the physiological phenomena of venous contrasting in the region of the shoulder and arm are examined. The remaining phlebograms with pathological findings are assessed according to different criteria, such as localisation and extent of venous vascular occlusion, visualisation of vascular clot and formation of collaterals resulting in collateral circulation.
A sequential combination of methotrexate and 5-fluorouracil was used for treatment of 20 patients with metastasizing colorectal carcinomas. Pretreatment with 5-fluorouracil had been given to five patients. While the chemotherapeutically pretreated patients showed two partial remissions, two minimal remissions and one progression, the remaining patients showed one full remission, six partial remissions, five minimal remissions and three progressions. The average partial remission time of these patients was 7,9 months. The average survival time will probably be more than one year. The toxicity of treatment was slight.
A 693 basepair cloned fragment of bacteriophage T4 DNA, which supports specifically growth of T4 amber mutants in gene 57, has been sequenced. A polypeptide can be deduced from this sequence, that is either 54 or 60 amino acids long depending which of two AUG codons, 18 nucleotides apart, are used for initiation. The size of this deduced polypeptide is compatible with the size of a single polypeptide (based on polyacrylamide gel electrophoresis) synthesized in vivo in E. coli under the direction of the cloned T4 DNA fragment.
A group of 227 cases of non-Hodgkin's lymphoma included seven favorable and four unfavorable histologic classes with collective median survival times of 83 and 16 months, respectively. The favorable group included three follicular subgroups (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt's noncleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse subgroups (plasmacytoid lymphocytic, mixed, and small and large noncleaved). There were significant differences in collective median survivals between patients in Stage I--II and those in Stage III--IV in both the favorable group (not reached, NR versus 62 months, P less than 0.001) and the unfavorable group (57 months versus 12 months, P less than 0.01). The incidence of complete response to primary treatment was higher in the favorable than in the unfavorable group (75% versus 56%, P = 0.002) and in those with limited as compared with advanced disease. Complete responders in both prognostic groups had longer survival times than did partial or minimal responders. A significant difference in median complete remission duration was found between responders in Stage I--II versus Stages III-IV in the favorable group (not reached versus 40 months, P = 0.001) but not in the unfavorable one (56 months versus 22 months, P greater than 0.05). The absence of relapses after 41 months among complete responders in the favorable but not in the unfavorable group suggests a potential for cure in a proportion of cases from the former group. The incidence of complete response was lower and median remission duration was shorter after secondary as compared with primary treatment. The results of this study confirm the prognostic value of the Lukes and Collins classification system and the importance of initial staging and of achieving a complete response to primary treatment in both the favorable and unfavorable lymphomas.
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Thirty-nine patients with primary amenorrhoea were examined, with twelve of them exhibiting chromosomal aberrations. The classical chromosomal pattern of Turner's syndrome with 45,XO was exhibited by seven patients, while mosaicism was displayed in the karyogram of three. A typical iso-X-chromosome was established from a young girl without Turner's stigmata. Genuine gonadal dysgenesis without any chromosomal abnormality was recorded from four cases by means of ovarian biopsy through laparoscopy.
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Histologic groups in 231 cases of malignant lymphoma were correlated with survival data at 100 months from the time of initiation of the study. Patients in the first two decades of life fared comparably with adults, but those over 60 years of age showed a poorer survival trend. Seven favorable and four unfavorable histopathologic groups were found with collective median survivals of 83 and 16 months, respectively (P less than 0.001). The favorable group included three follicular classes (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt non-cleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse classes (plasmacytoid lymphocytic, mixed, and small and large non-cleaved). The group of 88 patients with follicular lymphoma had significantly longer overall survival than the group of 143 patients with diffuse lymphomas. No significant differences in survival were noted within three grades of follicular involvement. The favorable and unfavorable diffuse lymphomas had collective median survivals of 82 and 16 months, respectively (P = 0.01). Significant survival differences due to pattern of nodal involvement (P = 0.01) were found in patients with mixed and large non-cleaved cell lymphomas, but not in those with cleaved cell lymphomas. The group with large cleaved cells had significantly longer survival than those with large non-cleaved cells. Patients with mixed and large non-cleaved cell lymphomas of the same nodal pattern had similar survival data.
The aim of the study was to compare the combination 5-FU-carmustine with ftorafur-carmustine in the treatment of advanced gastrointestinal cancer. To this end, a prospective, multicenter, randomized trial was initiated. Part I of this trial showed that similar response rates can be obtained with 5-FU-carmustine and ftorafur-carmustine in 109 patients (32.7% versus 26.3%). However, median survival was better in patients treated with 5-FU-carmustine (307 days versus 163 days). Part II of the trial revealed that neither a higher dosage of ftorafur (2 g/m2/day X 5 days) nor the addition of vincristine to both regimens changed the previously obtained results significantly. Again, median survival was found to be better in patients treated with 5-FU combination chemotherapy (304 days versus 144 days). Both the 5-FU and the ftorafur combination were tolerated reasonably well. The results suggest that combination chemotherapy including 5-FU is superior to ftorafur at the applied dosages in terms of survival.
Formation of both the tail fiber and the baseplate of bacteriophage T4 depends on the product of T4 gene 57. A single amber mutation in that gene causes loss of two T4-specific proteins. Their molecular weights are 18,000 and about 6,000, respectively, based on their electrophoretic mobilities in SDS-polyacrylamide gels. E. coli carrying a cloned T4 DNA fragment of about 700 basepairs, which directs the synthesis of the smaller protein only, specifically supports the growth of gene 57 amber mutants. We conclude that the small protein is a functional product of gene 57.
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1. In six healthy volunteer subjects polydipsic water loading significantly increased urine volume from 1203 +/- 242 (SEM) to 5072 +/- 320 ml/24 h (P less than 0.001) with a significant decrease in urinary osmolality. This increase in urine volume by more than fourfold was associated with a slight increase in urinary excretion of prostaglandin E2 from 466 +/- 66 to 1017 +/- 174 pmol/24 h (P = 0.05). 2. In five patients with central diabetes insipidus mean urine volume of 10 838 +/- 107 ml/24 h was reduced to 1205 +/- 204 ml/24 h (P less than 0.001) by treatment with 1-desamino-8-arginine vasopressin (desamino-[Arg8]vasopressin; 15 microgram/day) with a significant rise in urinary osmolality. Desamino-[Arg8]vasopressin treatment was associated with a significant increase of suppressed urinary excretion of prostaglandin E2 (PGE2) in four of these patients from 246 +/- 66 to 2643 +/- 677 pmol/24 h (P less than 0.01). 3. Concomitant treatment with indomethacin in addition to desamino-[Arg8]vasopressin significantly suppressed urinary excretion of PGE2 and significantly increased urinary osmolality as compared with treatment with desamino-[Arg8]vasopressin alone. 4. Desamino-[Arg8]vasopressin significantly increased urinary excretion of adenosine 3':5'-cyclic monophosphate (cyclic AMP). However, there was no further change in urinary excretion of cyclic AMP during concomitant indomethacin treatment. 5. The results suggest that urine flow itself is not an important determinant of urinary PGE2 excretion. In patients with central diabetes insipidus the urinary concentrating response to desamino-[Arg8]vasopressin is enhanced during inhibition of prostaglandin synthesis without changes in urinary excretion of cyclic AMP.
The chloroplast genomes of Euglena gracilis and Spinacia oleracea were investigated in their compositional heterogeneity, by using different experimental approaches. Euglena chloroplast DNA has a dG + dC content of 28%. Preparations averaging 20 x 10(6) in molecular weight exhibit a gross heterogeneity in their elution profiles from hydroxyapatite and in their buoyant densities because the rRNA genes have a high rG + rC content. Finer analysis by melting, buoyant density of restriction fragments and micrococcal nuclease degradation have revealed an extended compositional heterogeneity. From micrococcal nuclease digestion data, approximately 30% of the chloroplast genome is as low as 12% in its dG + dC content, whereas 10% is higher than 60% dG + dC. Since the average dG + dC content of large restriction endonuclease fragments varied to a lesser extent, most of dA + dT-rich sequences must occur in short stretches interspersed with dG + dC-rich stretches. Spinach chloroplast DNA (dG + dC = 36.5%) did not exhibit any gross compositional heterogeneity in its hydroxyapatite elution or in its buoyant density profile. But the higher resolution methods of melting, bouyant densities of restriction fragments and micrococcal nuclease degradation revealed a high degree of heterogeneity which appears to be due to interspersion of short DNA stretches of different base composition. About 30% of genome is as low as 22% in dG + dC, while 10% is higher than 60% in dG + dC.
We report a case of a T-zone malignant lymphoma of a cervical lymph node developing in a 25-year-old man. Only 14% of the marrow was originally involved, but within two months massive, leukemic dissemination ensued. The blast cells were unable to bind sheep erythrocytes (E) but expressed human thymus leukemia antigen (HTLA) and common ALL-stem-cell (cALL) antigen and had high terminal deoxynucleotidyl transferase (TdT) and acid phosphatase activity. These findings suggest a malignant lymphoproliferative disorder of pre-T-cell type. Complete remission was achieved with intensive chemotherapy. Two months later, acute myelomonocytic leukemia was diagnosed; at this time, over 90% of the blast cells were peroxidase, sudan black, and chloracetate-esterase positive. Consistent with loss of high TdT activity and HTLA and cALL antigens, 86% of the blasts now expressed Ia-like antigens. Cytogenetic studies demonstrated hyperdiploidy. Reports of granulocytic leukemia in lymphoma are reviewed in the context of the above findings and the hypothesis that a leukemogenic factor affects a multipotential stem cell.
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