21 February, 2009

Dr. Arthur Kornberg's comment on Penicillin

Dr. Arthur Kornberg and his family ---- from the book "For the love 
of enzymes: The odyssey of a Biochemist. Harvard University Press. 
synthesis of a infectious phagea virus of bacteria in 1967) wrote 
about penicillin.

  Penicillin and other antibiotics are the most dramatic 
therapeutic advance in medicine in my lifetime. When I was a 
student and intern before the advent of antibiotics, the 
treatment of lobar pneumonia was discouraging ineffective. 
One out of four patients died. Subacute bacterial endocarditis 
was invariably fatal. Rheumatic fever and acute nephritis 
were prevent.        

Many people know that antibiotic therapy was not discovered 
at bedsides nor even in a clinical pharmacology laboratory. 
Bullrings in Spain have a statures of Alexander Fleming, 
who in 1929 noticed the inhibition of bacterial growth around 
penicillin mold contaminated his Petri plate.        

The apotheosis of Fleming gored bullfighters is exaggerated 
because the practical use of the penicillin mold was not 
discovered by Fleming. It took Ernst Chain, a biochemist, 
and Howard Florey, a pathologist, to apply this knowledge 
ten years later to isolate penicillin and demonstrated its 
clinical utility.        

   There is much more to the penicillin story than that. 
Basic inquiries and findings essential to Fleming's discovery 
started at least fifty years earlier. Fleming would never have 
made his observation without the agar Petri plate. But, more 
important, he would never have understood what he saw on 
the plate were it not for the firm foundations of bacteriology 
and immunology.       

One might assume that Chain and Florey undertook the 
isolation of penicillin because of its possible clinical potential. 
Not at all. With the encouragement of Florey, Chain started 
his research on penicillin only because he was curious about 
the dissolution of bacterial walls by enzymes such as lysozyme. 

He thought penicillin was an enzyme too and wanted to 
understand the mechanism of its action. He surprised to find 
that penicillin was a molecule small enough to pass readily 
through the pores of a dialysis membrane which stopped 
passage of molecules as large as enzymes. 

Penicillin was not enzyme at all. This discovery immediately 
presented the possibility that penicillin, as a low-molecular-
weight compound, could be administered as a drug to animals. 
With the technique of freeze-drying, which had just become 
available, Chain was able to concentrate and preserve 
penicillin and then to prove its therapeutic efficacy.       

  Why were Chain and Florey so quickly to test their very 
crude penicillin preparations for clinical efficacy?  Their 
prompt decision was likely conditioned by the discovery in 
the mid-1930s that sulfonamides inhibit microbes and yet are 
not toxic to animals. 

Thus, an agent could selectively interrupt growth of microbes 
without affecting the animal host, and this observation gave 
Chain and Florey the confidence to test their penicillin prepa-
rations in infected mice.       

It may also explain why Fleming, ten years earlier, believing 
that only the host immune system could combat infections, 
regarded chemotherapy as implausible and so failed to test 
his crude penicillin preparations for therapeutic value. 
I choose penicillin as an example of the importance of basic 
research because its history is so recent and dramatic.   

Arthur Kornberg: For the love of enzymes: The Odyssey of a 
Biochemist. Harvard University Press. 1991.

Any questions:  write to Keiji Hagiwara, MD

19 February, 2009

Haemophilus influenzae(2)

Photo )  Colonies of Haemophilus influenzae on the chocolate agar plate.
                 (Dr. Mizuno, Department  of Clinical Laboratory, Yamaguchi
                  University School of Medicine)

Photo )  Electron-microscopic graph of H. influenzae.
             The shape of this bacteria is round or rods like. Green colour was
             added later, not the real colour. 
             (Dr.Dennis Kunkel, Dennis Kunkel Microscopy, Inc, Kailua, HI)

Any questions:
             write to Keiji Hagiwara, MD
             Kami-Ube Pediatric Clinic,
             1) keijihagiwara@gmail.com   2) keiji-hagiwara@umin.ac.jp

10 February, 2009

Haemophilus influenzae (1)

Photo )  H. influenzae are observed inside of white blood cells.
               (Dr.Rebecca Buxton, Department of Pathology, University of Utah)
Photo ) H. influenzae in the sputum .
            (Dr. Rebecca Buxton, Department of Pathology, University of Utah)

Haemophilus influenzae

This bacteria( = Pfeiffer's bacilli) once thought to be a cause of  influenza(=Flu).

i) Microscopic findings: round or lods in shape, Gram stain(-)
ii)Type: divided into non-capsular type and capsular type.
             Capsular type:  Serovar (5 types; a, b, c, d, e, f )
                  ✭ type b is predominant, especially in acute meningitis and epiglottis.

iii) Type of diseases in childhood:
                   1) common cold: no data is  available.
                   2) otitis media:  non-capsular type is common.
                   3) acute epiglottis: very few in Japan.
                   4) bronchitis & pneumonia: non-capsular type is common.
                   5) meningitis: type b is dominant in Japan.

                        is available.

Any questions:  write to Keiji Hagiwara, MD
                         E-mail: keijihagiwara@gmail.com