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Objective: To investigate if there is a difference in response to tuberculosis treatment between HIV seronegative and HIV seropositive patients following two months of intensive phase tuberculosis treatment., Design: Prospective cohort study., Setting: St. Francis Leprosy Centre, south-east Uganda., Subjects: Four hundred fifty seven patients with never previously treated sputum smear-positive tuberculosis admitted during a two-year period in 1991/1993., Intervention: Intensive phase treatment with streptomycin, isoniazid, rifampicin and pyrazinamide., Main Outcome Measures: Sputum conversion from a positive to a negative smear at eight weeks of treatment., Results: HIV seropositivity prevalence was 28%. Among HIV seronegative patients, conversion to a negative smear status occurred in 76% persons compared to 78% in HIV seropositive patients. This difference was not statistically significant (OR = 0.9; 95% CI, 0.6-1.5). HIV seropositive patients, however, were more likely to die (p = 0.017). A high prevalence of resistance to isoniazid and streptomycin was found. Isoniazid resistance was more likely in HIV seronegative patients with M. tuberculosis strains compared to HIV seropositive persons (p < 0.005). Initial resistance to antituberculosis drugs did not have a significant effect on smear conversion., Conclusion: This study demonstrates that HIV-seropositive status is not a principal factor in delaying sputum conversion among patients receiving intensive phase tuberculosis treatment.

The Mycobacterium tuberculosis complex includes M. tuberculosis, M. bovis, M. africanum, and M. microti. Most clinical isolates are M. tuberculosis or M. bovis. These species can be distinguished by phenotypes and genotypes. However, there is no simple definition of M. africanum, and some authors question the validity of this species. We analyzed 17 human isolates from Sierra Leone, identified as M. africanum by biochemical and growth characteristics. We sequenced polymorphic genes and intergenic regions. We amplified DNA from six loci with variable numbers of tandem repeats (VNTRs) and determined the exact number of repeats at each locus in each strain. All M. africanum isolates had the ancestral CTG Leu at katG codon 463. Drug-resistant M. africanum isolates had katG and rpoB mutations similar to those found in drug-resistant M. bovis and M. tuberculosis. Fourteen Sierra Leone M. africanum isolates (designated group A) had katG codon 203 ACC Thr, also found in M. africanumT (the T indicates type strain) from Senegal. Group A isolates clustered with M. africanumT by VNTR analysis. Three M. africanum isolates (group B) had katG codon 203 ACT Thr, found in M. tuberculosisT, and clustered with M. tuberculosisT by VNTR analysis. Phenotypic identification of M. africanum yielded a heterogeneous collection of strains. Genotypic analyses identified a cluster (M. africanum group A) which included M. africanumT and was distinct from the rest of the M. tuberculosis complex. Future studies of M. africanum should include both phenotypic and genotypic analyses.

Setting: Mutations in two genes of Mycobacterium tuberculosis, inhA and katG, are known to correlate with resistance to isoniazid (INH)., Objective: To determine which mutation or mutations are the most predictive for INH resistance and the most frequent ones in such isolates. Further, to propose a simple and generally applicable method for their detection., Design: Codons 94 and 95 in the inhA gene and codons 315 and 463 in the katG gene were characterized in 50 INH-resistant and 12 INH-sensitive isolates from Germany and Sierra Leone., Results: Mutations in codon 315 of the katG gene were detected in 27 of the INH-resistant and none of the INH-sensitive isolates. All mutations in this codon altered an AciI restriction enzyme site. No mutations were found in the investigated codons of the inhA gene., Conclusion: We propose that most INH resistances can be rapidly predicted by a simple AciI restriction enzyme digest of a polymerase chain reaction (PCR)-amplified katG fragment.

The effectiveness of culture-independent resistance predictions by molecular techniques is dependent on the number and the frequency of accessible resistance-associated genomic mutations. We have characterized an rpoB gene region involved in rifampicin resistance in 49 Mycobacterium tuberculosis isolates resistant to rifampicin from Germany and Sierra Leone. The determined frequencies of mutations differed between both countries of origins as well as with respect to previously reported distributions of resistance mutations. It is concluded that at least for some isolates the acquisition of mutations leading to rifampicin resistance in clinical samples of M. tuberculosis is a non-random process which may lead to a geographical and temporal dependence of the sensitivities of molecular typing techniques for rifampicin resistance predictions.

About 95% of individuals who come in contact with M. leprae do not develop overt disease. The clinical form of the disease correlates with the T-cell mediated immune response of the host rather the direct damage caused by bacilli. We review the current aspects of epidemiology, transmission, bacteriology, clinical features, reactions, diagnosis, chemotherapy and treatment of reactions.

Specific mutations associated with resistance to streptomycin (SM) in Mycobacterium tuberculosis suggest themselves for its rapid prediction. However, as with any diagnostic test, their predictive values are dependent on their prevalences. In this report, SM resistance associated mutations in the rrs and rpsL genes of 25 SM resistant isolates from Germany and 25 SM resistant isolates from Sierra Leone were characterized and compared. Mutations in the rrs gene were infrequent in isolates from both localities (20% and 12%, respectively) and thus of limited predictive values. In contrast, rpsL mutations were found in 48% of the German isolates but only in 24% of the isolates from Sierra Leone. It is concluded that the predictive values of mutations in this gene may vary significantly with the origin of the samples under investigation.

95% of individuals who come in contact with M. leprae do not develop an overt disease. It begins as an indeterminate form that may undergo spontaneous cure or may progress to different forms of leprosy (TT, BT, unstable form of BB, BL, or LL). The clinical form of the disease correlates with the T cell mediated immune response rather than to the direct damage caused by the bacilli. The lack of cellular immunity in lepromatous patients relates specifically to M. leprae. Current aspects of etiology, transmission, epidemiology, classification, clinical features, immunopathology, chemotherapy, treatment of reactions, immunotherapy and vaccination are elucidated and discussed.

A small amount of antitryptic activity is detectable in the supernatant of deproteinized human serum. Preincubation of serum with trypsin causes an increase in acid-stable antitryptic activity. This rise in activity depends on the inter alpha-trypsin inhibitor concentration. The native inhibitor present in normal sera, and in higher concentrations in sera of patients with nephropathies, and the trypsin-liberated inhibitor show immunological cross reaction with antibodies to the serum inter-alpha-trypsin inhibitor. The two inhibitors differ in molecular weight and electrophoretic mobility. The physiological inhibitor (I-34), with a molecular weight of 34 000 and a high carbohydrate content, can be transformed by trypsin into an inhibitor (I-17) with a molecular weight of 17 000. This inhibitor is identical with the inhibitors liberated by trypsin from serum or from purified inter-alpha-trypsin inhibitor. The acid-stable inhibitor from urine is identical with the physiological serum inhibitor. Analogously, this inhibitor is transformed by trypsin into the inhibitor with a molecular weight of 17 000. We conclude that the inter-alpha-trypsin inhibitor is the precursor of both the physiological and the trypsin-liberated inhibitor. By a mechanism as yet unknown, but most likely a limited proteolysis, the secreted inhibitor is liberated from the high molecular weight precursor. In contrast to the monospecific trypsin-inhibiting precursor, the physiological and artificially liberated inhibitors are trypsin/chymotrypsin/plasmin inhibitors.

A short digestion with excess of trypsin releases an inhibitor with an apparent molecular weight of 14,000 from both the inter-alpha-trypsin inhibitor and the ITI-related acid-stable inhibitor. The amino acid sequence of this inhibitor was determined. The inhibitor is composed of two covalently linked homologous Kunitz-type domains. One domain has antitryptic activity, as reported. This paper characterizes the second, inactive domain as also of the Kunitz type.

The protein composition of human parotid saliva was explored by means of one- and two-dimensional immunelectrophoresis as well as by a modified Ouchterolony-technique and discelectrophoresis, where usually at least 14 components of parotid-saliva-proteins can be differentiated. According to the results of immunelectrophoresis and discelectrophoresis, the kind and number of protein components are interindividually constant, yet, there are great interindividual differences concerning the concentration of the single components.

Plasma membranes were isolated in high yield from Xenopus gastrulae by repeated sedimentation in discontinuous sucrose gradients. Most of the yolk was separated by lowspeed sedimentation before centrifugation on the discontinuous sucrose gradients. The isolation of plasma membranes was followed by covalent labelling of the surface of dissociated gastrula cells with diazoniobenzene sulphonate, by electron microscopy and the distribution of enzymatic markers. The isolated plasma membranes have a low neural inducing activity as compared to other cell constituents.

Canine submandibular glands contain 3 polyvalent, double-headed proteinase inhibitors. The amino acid sequences of the two main inhibitors were determined. They differ only in the substitution of one Lys for a Glu residue. The inhibitor molecules are composed of two halves (domains), one antitryptic and one antichymotryptic. The two domains are covalently linked by 3 amino acid residues. The domains are structurally related to each other and to the sequenced monovalent secretory pancreatic trypsin inhibitors.

Fractionated human parotid saliva from normal persons was separated by column-acryamid-gel discelectrophoresis. Flow rates, electrolyte-concentrations and total protein content of the stimulated and unstimulated parotid-secretion were determined simultaneously. Significant patterns of proteincomposition were found for stimulated and unstimulated parotid saliva. Most typical changes of protein bands were found in the anodal near gel region, within a group of four bands, called by us f, g, h and i. In the cathodal near gel region as well significant changes in the bands a, b, c and d were found; by glycoprotein staining these bands showed good staining.

In comparison to former investigations in pleomorphic adenoms and Wharthin tumours in the present paper secretion of IgA, lysozyme in correlation to flowrate and total secretion in glands with malignant tumours, inflammations and Sialadenosis were estimated. Thereby 12 patients with malignomas of the parotid gland, 11 patients with chronic parotitis and 12 with sialadenoses were examined. The following results were found: 1. The concentration of protein, IgA and Lysozym is significantly higher than in normal glands and in glands with pleomorphic adenomas and Wharthin tumours. 2. Differentialdiagnosis of Sialadenitis and Sialadenosis of parotid glands is possible by estimating the examined parameters. Thereby in glands with sialadenosis flowrate is higher than in normal glands, and significant lower in glands with sialadenitis. Moreover concentrations of IgA and Lysozyme and protein in glands with sialadenitis are evaluated.

In comparison to normal gland secretions 28 patients with mixed tumors of the parotid glands are examined. Thereby fractionated secretions under rest and stimulation are collected and estimations of flowrate, protein-, lysozyme- and immunglobulin A-secretion are done. The following results are remarkable: 1. After pilocarpinstimulation response of the glands 20 to 30 min later than in normal glands. 2. Protein-secretion is diminished in rest and under stimulation. 3. Immunglobulin A and lysozyme secretion show a greater range than normal glands under rest and stimulation.

By means of acrylamidgelectrophoresis parotid secretions of patients with acute and chronic parotitis were examined. Thereby significant changes in protein patterns of electrophoretic separation were found. Especially two bands are described in detail. One in the cathodal near gel region, the isoamylases, and the otherone in the anodal part of the gel, identified as albumin. In rest and under stimulation these bands show signficant changes compared to normal secretions. Furthermore information about the capacity of the parotid gland parenchyma is won by observing the changes of amylase bands in rest and under stimulation in chronic parotitis without actute exacerbations. The amylase shows a remarked decreased secretion in chronic parotitis under stimulation corresponding to parenchymalteration. The same happens with the albuminexcretion as parameter for ductlesions. In chronic parotitis albmuninexcretion goes parallel to duct changes in sialography. Therefore by discelectrophoretic separation of native parotid saliva a helpful mean for diagnostic use is given, besides sialography and scintigraphy.