Crop wild relative populations of Beta vulgaris allow direct mapping of agronomically important genes.

Rapid identification of agronomically important genes is of pivotal interest for crop breeding. One source of such genes are crop wild relative (CWR) populations. Here we used a CWR population of <200 wild beets (B. vulgaris ssp. maritima), sampled in their natural habitat, to identify the sugar beet (Beta vulgaris ssp. vulgaris) resistance gene Rz2 with a modified version of mapping-by-sequencing (MBS). For that, we generated a draft genome sequence of the wild beet. Our results show the importance of preserving CWR in situ and demonstrate the great potential of CWR for rapid discovery of causal genes relevant for crop improvement. The candidate gene for Rz2 was identified by MBS and subsequently corroborated via RNA interference (RNAi). Rz2 encodes a CC-NB-LRR protein. Access to the DNA sequence of Rz2 opens the path to improvement of resistance towards rhizomania not only by marker-assisted breeding but also by genome editing.

An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.

A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma.

In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. I. Microbial deepoxidation and subsequent isomerization of deltamycins A1, A2, A3, A4 (carbomycin A) and X.

Carbomycin A (deltamycin A4) was deepoxidized to carbomycin A P1 by Streptomyces halstedii subsp. deltae (a deltamycins producer), favorably under anaerobic conditions. Carbomycin A P1 was spontaneously converted to geometric isomers designated carbomycins A P2 and A P3. This type of deepoxidation and subsequent isomerization was not limited to carbomycin A, but generally occurrable in other 16-membered epoxyenone macrolide compounds. Many bacteria and actinomycetes were also found to have an ability to deepoxidize deltamycins reductively. The chemical structures of carbomycins A P1, A P2 and A P3 were elucidated as shown in Fig. 3.

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. III. In vitro and in vivo evaluation of deepoxidation products of carbomycin A, deltamycin A1, 4"-phenylacetyldeltamycin, angolamycin and rosamicin.

Deepoxidation products P1, P2 and P3 of carbomycin A, deltamycin A1 and 4"-phenylacetyldeltamycin showed high in vitro antibacterial and antimycoplasmal activities which were comparable to those of the respective parent compounds. By contrast, the in vitro antimicrobial potencies of angolamycin P1 and rosamicin P1 were about ten-fold lower than those of the parent macrolides. In mice, the increase in the plasma levels of the epoxyenone macrolides due to deepoxidation was highly significant with the P1, P2 and P3 derivatives of carbomycin A and 4"-phenylacetyldeltamycin, whereas angolamycin P1 gave a moderately-improved plasma level compared with angolamycin.

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. II. Chemical deepoxidation by dissolving metal reduction.

16-Membered epoxyenone macrolide antibiotics were reductively deepoxidized with dissolving metals such as zinc. Angolamycin and rosamicin which have a methyl substituent at C-12 in the epoxyenone structure were deepoxidized, but not isomerized further to the geometric isomers P2 and P3.

Limitations of the oral calcium loading test in the management of the recurrent calcareous renal stone former.

Twenty-two patients with idiopathic hypercalciuria were evaluated using an oral calcium loading test and compared with 20 normal controls. Following a 12-hour overnight fast, all subjects collected a two-hour urine sample after which they received 1 g elemental calcium as galacto-gluconate in milk. Two further two-hour urine collections were obtained consecutively following the oral calcium load. In the fasting state, 4 (18%) of the 22 patients had urinary calcium excretion (UCaE) above normal, but none had elevated iPTH or urinary cAMP values. After calcium loading, only 10 (45%) of the 22 patients had delta UCaE greater than controls (delta = difference in UCaE between third and first urine samples). We conclude that despite demonstrable differences between the mean values of patient and control groups with respect to the UCaE following calcium loading, the large overlap of values negates the clinical usefulness of such procedures in the routine management of individual patients. The definition of renal leak hypercalciuria based on a high fasting UCaE alone remains of uncertain significance.

The faculty and continuing medical education: an attitude study.

Meager or nonexistent faculty reward systems hamper continuing medical education (CME) programs conducted by U.S. medial schools. In light of a growing number of mandatory CME regulations and a consequent increase in physician attendance of CME programs, the need for a competent faculty is apparent. A survey of faculty members designed to ascertain the importance of a faculty reward system was conducted by the University of Washington Division of Continuing Medical Education. Results reveal that faculty members are twice as likely to teach in CME programs outside of the university system as within the system. Survey respondents of nonprofessor rand considered faculty advancement the single greatest source of encouragement to participate in CME programs, yet this participation is seldom considered by the university in evaluations for promotion or tenure. If medical schools are to accept a responsibility for the continuing education of medical professionals, a commitment to provide adequate faculty incentive is imperative.