Botulinum versus tetanus neurotoxins: Why is botulinum neurotoxin but not tetanus neurotoxin a food poison?

Botulinum and tetanus neurotoxins, produced by Clostridium botulinum and Clostridium tetani, respectively, are the most poisonous poisons known to mankind. Although botulinum and tetanus neurotoxins share several characteristics, such as similar mol. wts, similar macrostructure, virtually identical mode of action, and a strong amino acid sequence homology, the two neurotoxins differ in one very significant way; only botulinum neurotoxin is a food poison. Factors responsible for the food poisoning potential of botulinum neurotoxins seem to be a group of complexing proteins that are also produced by C. botulinum, and are known to associate with the neurotoxin. Translation products of nucleotide sequences upstream to the neurotoxin genes of serotypes A, B, C, D, E and F botulinum neurotoxin reveal the location of genes for one of the complexing proteins that could be transcribed as polycistronic mRNA to include neurotoxin sequences. No such protein seems to be present in C. tetani, suggesting that the lack of complexing proteins might be responsible for tetanus not being a food poison.     

The epidemiology of psychosis: the Suffolk County Mental Health Project.

This article describes the rationale, aims, and methodology of an epidemiological study of psychosis being conducted in Suffolk County, New York. A sample of first-admission patients is drawn from 10 inpatient and 25 outpatient facilities. Diagnostic psychosocial interviews are conducted shortly after admission to treatment, and at 6- and 24-month followup. Consensus diagnoses are made after each interview. Demographic and clinical background characteristics of the first 250 subjects enrolled over a 2-year period are presented here. The response rate was 76 percent. Based on the initial interview, 75 percent of subjects received a diagnosis involving psychosis. The three most common diagnoses were schizophrenia, bipolar disorder with psychotic features, and major depression with psychotic features. Among subjects with psychosis, 58 percent of males and 29 percent of females had a history of substance abuse/dependence. Gender differences were found on several background and clinical characteristics. Males were somewhat younger, less likely to have ever married, and had less education. Although the median length of hospitalization was the same for females and males (27 days), females were more likely to be hospitalized within 1 month of the occurrence of their first psychotic symptom (60% of females compared to 37% of males). Subjects with schizophrenia-related disorders were significantly more impaired on an assessment of negative symptoms than were affectively ill subjects, but clinical ratings of depression were not significantly different across diagnostic groups.     

Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure.

OBJECTIVES: We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF). BACKGROUND: Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients. METHODS: We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay. RESULTS: Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects. CONCLUSIONS: These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.     

Natural history of experimental pulmonary atelectasis in dogs with closed chest

In order to establish an animal model of pulmonary vasoconstriction we followed the time course of intrapulmonary shunt (Qs/Qt) in a canine model of lobar atelectasis with closed chest. Ten mongrel dogs were studied. Bronchial occlusion of the right lower lobe (RLL) was performed by inflating the balloon of a Foley catheter placed through a rigid bronchoscopy. Analysis of variance was used for statistical analysis. (15 minutes) After occlusion Qs/Qt reached its maximum increasing from 8.2 +/- 3.6 to 29.7 +/- 11.7% (p less than 0.05) and PaO2 decreased from 357 +/- 49 to 100 +/- 43 mm Hg (p less than 0.05). Afterwards, there was a progressive decline of Qs/QT accompanied by an also progressive increase in PaO2. At the end of the experiment (3 hrs post atelectasis) Qs/Qt was 11.2 +/- 4.9 and PaO2 251 +/- 124 mm Hg (p less than 0.05). Pulmonary vascular resistance increased post atelectasis from 439 +/- 168 to 598 +/- 256 d.s.cm-5 (p less than 0.05). Complete atelectasis of the RLL was confirmed postmortem. As the changes in Qs/Qt and PaO2 did not parallel the change in cardiac output we conclude that the mechanism of decrease in Qs/Qt was hypoxic vasoconstriction.     

Medical and surgical management male infertility.

Male infertility is the result of a variety of highly treatable conditions. The critical step in treating male infertility is to evaluate properly every male partner of an infertile couple and to generate the proper treatment strategy. There are many medical and surgical options that can help most couples overcome male factor infertility. Male infertility can most easily be broken down into problems of sperm production (testicular dysfunction) and problems of sperm transport (obstruction). When applicable, medical therapies are used as an initial strategy to improve sperm production or as a preliminary therapy to boost production transiently in anticipation of a surgical sperm retrieval attempt. A range of surgical options is available to correct varicoceles, reconstruct the obstructed system, or retrieve sperm for assisted reproduction.