Adenosine deaminase deficiency in adults.

Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combined immunodeficiency. She had frequent infections, lymphopenia, and recurrent hepatitis as a child but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, and hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal immune function, was identified after his niece died of SCID. Both patients lacked erythrocyte ADA activity but had only modestly elevated deoxyadenosine nucleotides. Both were heteroallelic for missense mutations: patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A215T. Three of these mutations eliminated ADA activity, but A215T reduced activity by only 85%. Owing to a single nucleotide change in the middle of exon 7, A215T also appeared to induce exon 7 skipping. ADA deficiency is treatable and should be considered in older patients with unexplained lymphopenia and immune deficiency, who may also manifest autoimmunity or unexplained hepatobiliary disease. Metabolic status and genotype may help in assessing prognosis of more mildly affected patients.

[Tetanus--the forgotten disease].

Tetanus is preventable by proper immunization, which has almost eradicated the disease in countries with a high standard of living. However, the disease is still prevalent even in the most advanced countries and it often appears in the elderly. We emphasize this fact and alert primary care physicians, and duty physicians in emergency rooms, to the possibility of tetanus developing in older patients. Because of their age, they often do not remember when they last had tetanus immunization, nor are records always adequate. We point out the necessity and feasibility of incorporating a special immunization review program for the elderly, including a cost-benefit analysis.

[Disseminated tuberculosis with a multiresistant strain of Mycobacterium tuberculosis in an HIV-infected Swiss male]. / Disseminierte Tuberkulose mit einem multiresistenten Stamm von Mycobacterium tuberculosis bei einem HIV-infizierten Schweizer.

Multidrug-resistant M. tuberculosis in HIV-infected people has not yet been reported in Switzerland, and there have been no nosocomial epidemics as they have recently occurred in the USA. We present the case of a 38-ear-old HIV-infected man who developed disseminated tuberculosis as AIDS-defining disease. Initially he was treated with isoniazid, pyrazinamide and rifampin. Due to the emergence of resistance to isoniazid and streptomycin, ethambutol was added for one month. Later the therapy was changed back to the initial three drugs. The patient responded well to this therapy, but five months later developed a relapse. In addition to the originally diagnosed double-drug resistance, a reduced susceptibility to rifampin appeared. Ethambutol, ciprofloxacin and amikacin were added to the original three-drug regimen. This resulted in rapid clinical improvement, although sputum cultures remained positive for M. tuberculosis two months later. This isolate was resistant to pyrazinamide. For that reason pyrazinamide was replaced by clofazimine. 14 months after diagnosis the patient died of hepatic failure. Because there was a delay in isolation of one week, 37 potentially exposed health care workers were tested by the Mantoux skin test. No conversions were observed. This case report demonstrates that tuberculosis in HIV-infected patients in Switzerland may be caused by multidrug-resistant M. tuberculosis. We propose that until the results of a susceptibility assay are known, a four-drug combination should be used initially in this patient group.

The structure of acetomycin. Spectroscopic characterization and X-ray analysis of a bromo derivative.

Acetomycin (1a), known since 1958, has been further characterized by NMR and CD spectra. The 3-acetyl side chain of 1a is reduced selectively by sodium cyanoborohydride yielding the diastereomeric alcohols 2a and 3a, which were esterified to the crystalline bromoacetates 2c and 3c. The structure and absolute configuration of 3c was determined by X-ray analysis. From these data the absolute configuration of 1a followed as 3S, 4S, 5R.

3-Hydroxyrifamycin S and further novel ansamycins from a recombinant strain R-21 of Nocardia mediterranei.

The structures of 3-hydroxyrifamycin S and six further novel ansamycins isolated from the recombinant strain R-21 of Nocardia mediterranei were identified by spectroscopic methods. Three types of structure were distinguished: Type 1: Ansamycins of the rifamycin S type Type 2: Ansamycins of the rifamycin G type Type 3: Ansamycins of the rifamycin W type.

A genetic approach to the biosynthesis of the rifamycin-chromophore in Nocardia mediterranei. III. Isolation and identification of an early aromatic ansamycin-precursor containing the seven-carbon amino starter-unit and three initial acetate/propionate-units of the ansa chain.

A number of rifamycin non-producing UV-mutants derived from Nocardia mediterranei strains N813 (rifamycin B producer) and A10 (aro--mutant excreting shikimate derived from strain N813) were found to accumulate an identical complex of aromatic components instead of rifamycin B. The main component of this aromatic complex, product P8/1-OG, was isolated from six of these P--mutant strains and identified spectroscopically as a very early precursor in the biosynthesis of rifamycins.

Papulacandins, a new family of antibiotics with antifungal activity. Structures of papulacandins A, B, C and D.

The structures of the papulacandins A, B, C and D, new antibiotics of Papularia sphaerosperma have been established by means of spectral analysis and degradation reactions. Base catalysed hydrolysis of the main product papulacandin B (1) gave two new hydroxylated long-chain unsaturated fatty acids 5 and 6 along with a hitherto unknown spirocyclic diglycoside 7. The structure of 7 was determined by further degradation reactions. The positions of attachment of the two fatty acids to the spirocyclic diglycoside 7 through ester-bonds were established by selective base catalysed hydrolysis of 1 and spectral analysis of 1 and some derivatives and degradation products thereof. The structures of papulacandin A (2), papulacandin C (3) and papulacandin D (4) were determined in an analogous way.

Early intermediates in the biosynthesis of ansamycins. III. Isolation and identification of further 8-deoxyansamycins of the rifamycin-type.

A number of minor compounds were isolated from fermentations of the protorifamycin I producing strain Nocardia mediterranei F 1/24(1,2)) and identified by means of chemical and spectroscopic methods. Two types of structures were identified: Type 1: modified protorifamycins (derived from protorifamycin I) Type 2: defective rifamycins (8-deoxyrifamycins).

Early intermediates in the biosynthesis of ansamycins. II. Isolation and identification of proansamycin B-M1 and protorifamycin i-M1.

Proansamycin B-M1 and protorifamycin I-M1 were isolated as minor compounds from fermentations of the protorifamycin I producing strain Nocardia mediterranei F 1/24, identified by means of chemical and spectroscopic methods and shown to be degradation products of the hypothetical proansamycin B postulated in part I of this series of papers and of protorifamycin I, respectively.