Syphilis. An algorithm.
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Biomedical subjects
Publications and source records attributed to T J Lee.
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The structure of acid protease from Endothia parasitica in strongly cross-linked form is compared with that of the untreated protein at 2.45-a resolution. The only observed conformation change introduced by the cross-linking reaction is at the N terminal. Otherwise the two main chain structures are essentially identical. Approximately 2 molecules of the inhibitor, 1,2-epoxy-3-(p-nitrophenoxy)propane, are found to be incorporated into each protein molecule. They are covalently bound to the two aspartic residues at the active center.
The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.
We summarize data from 24 previously described or newly diagnosed cases of homozygous deficiency of the sixth, seventh, or eighth components of complement. Thirteen of 24 patients had at least one episode, and usually two or more episodes of Neisseria meningitidis or Neisseria gonorrhoeae bacteremia, or both. Deficiency of C6, C7, or C8 is a meaningful risk factor for repeated neisserial bacteremia; conversely, hemolytic complement studies are indicated in patients who develop recurrent neisserial infections. When a person with C6, C7, or C8 deficiency is identified, family members should also be studied.
Mucocutaneous lymph node syndrome (MLNS) is an acute febrile illness of unknown cause first described in Japan but more recently reported in the United States. The mean age in confirmed cases was 3.8 years (range, 3 months to 13 years), and the mortality is 1% to 2% when associated with coronary artery thrombosis and aneurysm. We describe the first case of MLNS in a young adult, with the additional clinical finding of associated arthritis.
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The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.
Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, gamma-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response.
Permanganate-fixed vasa deferentia from rats were examined for the presence of nexal-like contacts by electron microscopy. There was a significantly greater incidence of nexuses (2X) in chronically denervated tissues (5-7 days) but not in tissues from reserpine-pretreated animals (1.0 mg/kg/day for 5-7 days). The results suggest that an increase in nexal regions may not be a general feature of postjunctional supersensitivity but rather may contribute to other denervation-induced changes in contractile response.
We have determined that isolates of Neisseria gonorrhoeae from patients with disseminated gonococcal infection (DGI) are different from randomly collected isolates from patients with uncomplicated (local) disease. Our comparison was based on the six phenotypic properties of: sensitivity to penicillin (PenS), erythromycin, and streptomycin; resistance to the bactericidal effects of pooled human sera; requirements for arginine, hypoxanthine, and uracil (AHU-); and sensitivity to toxic agar. Although the marked association among these traits made analysis difficult, several factors independently related to virulence were defined. The DGI isolates were significnatly more PenS and resistant to serum, even when the other variables were held constant. An apparent correlation between AHU- auxotype and virulence was shown to be due to the PenS property of most AHU- isolates. Thus, certain mutations to antibiotic resistance as well as susceptibility to sera, may result in loss of virulence in the gonococcus, perhaps through alteration of cell envelope structure.
A patient with post-traumatic seizure disorder developed lymphadenopathy, exfoliative dermatitis, and hepatic failure while on diphenylhydantoin therapy and died in hepatic coma. Autopsy disclosed massive hepatic necrosis. The clinical and pathological pictures are similar to the six previously reported cases of diphenylhydantoin-induced hepatic necrosis, with the exception of the time of onset of hepatic failure, which is explained. The cause of such hepatotoxicity is unknown, although hypersensitivity is postulated. It appears that studies of liver function in patients receiving diphenylhydantion are indicated to assess the true indicence of hepatocellular injury.
Rabbit basilar artery rings are normally relatively unresponsive to transmural stimulation of their sympathetic nerve supply. However, in the presence of histamine (0.55 muM), contractile responses to nerve stimulation were markedly increased. Norepinephrine and serotonin concentrations that produce 50% of a maximum contractile response (ED50) were considerably decreased in the presence of histamine; maximum responses to both norepinephrine and serotonin were increased. Although a prejunctional effecto of histamine has not been eliminated, potentiation of responses to transmural nerve stimulation is probably due to an increase in smooth muscle responsiveness to norepinephrine. In rabbit saphenous artery rings, histamine produced a qualitatively similar potentiation of responses to nerve stimulation, norepinephrine, and serotonin except that maximum responses were not increased. Serotonin (0.084 muM) did nog potentiate contractile responses of the basilar artery to transmural nerve stimulation or norepinephrine. Since histamine and serotonin are released from rabbit platelets in response to tissue injury the synergistic effect of these agents on vascular smooth muscle contraction might be advantageous in minimizing hemorrhage. But such a response could also be deleterious if the effects of these vasoconstrictors were prolonged.
Chronic postganglionic denervation of the rate vas deferens produces an increase in the sensitivity of the in vitro smooth muscle to norepinephrine, methoxamine, acetylcholine, potassium and electrical stimulation. The maximal contractile response to norepinephrine and acetylcholine is increased but the maximal response to potassium or electrical stimulation is not affected. In addition, the vas deferens becomes spontaneously active after denervation. The spontaneous contractions are not prevented by tetrodotoxin, phentolamine or atropine. The appearance and magnitude of the spontaneous contractions are temporally correlated with the development of postjunctional supersensitivity. At a given time after denervation there is a significant correlation between the magnitude of the spontaneous contractions and the sensitivity to norepinephrine, i.e., the sensitivity to norepinephrine being greatest in those tissues with the largest spontaneous contractions. There is an inverse relationship between the magnitude of the spontaneous contractions and the endogenous norepinephrine concentration. Pretreatment of rats with reserpine (1. 0 mg/kg/day for 5-7 days) results in supersensitivity of the vas deferens ,o norepinephrine and acetylcholine. Those tissues obtained from reserpine-pretreated rats which are supersensitive are also spontaneously active. It is concluded that the -ppearance of spontaneous contractions in the rat vas deferens is an index of postjunctional supersensitivity.
The effect of postganglionic denervation on the incidence of nexal contacts in the smooth muscle of the rat vas deferens was investigated. The chronically denervated tissue exhibited twice as many nexuses as control. This increase in the incidence of cell contacts may contribute to the supersensitivity and/or the increase in maximum response of the denervated vas deferens. The effects of denervation, decentralization, and pretreatment with reserpine on the concentration of adenosine triphosphate (ATP) in vasa deferentia of rats and guinea pigs were also investigated. One day after denervation there was a substantial decrease in the endogenous norepinephrine and ATP concentrations. The norepinephrine concentration remained low (less than 10% of control) throughout subsequent days (up to 14 days) whereas the ATP concentration, after the first postoperative day, rose significantly. The rise in ATP concentration was temporally correlated with the development of postjunctional supersensitivity. Decentralization and pretreatment with reserpine both resulted in a significant increase in ATP concentration which preceded by 2 to 3 days a significant increase in sensitivity of the vas deferens. It appears that a change in the tissue concentration of ATP may be one of the initial events that occurs following interruption of the neural contact to the smooth muscle of the vas deferens.